Accuracy of two different voxel sizes for presurgical evaluation of mandibular osteotomy.

The aim of this study was to compare the accuracy of two different voxel resolutions for the preoperative assessment of mandibular osteotomies. The study was conducted on 37 dry adult human mandibles. To obtain measurement standardization, heated gutta-percha cones were placed on the dry mandibles to mark 20 anatomical points. These cones were used for all measurement groups. Cone beam computerized tomography (CBCT) scans of the mandibles were made using 0.200mm3 and 0.400mm3 voxel sizes (Planmeca Promex-3D Helsinki, Finland). The results obtained from these two groups were compared with physical measurements obtained using a digital calliper, in order to analyze their predictive value. In the study, one voxel size did not have supremacy over the other in terms of accuracy. For mandibular osteotomies, 0.400mm3 voxel size can be preferred because of lower radiation dose.

False positive 18F-FDG PET scan in adrenal oncocytoma.

18F-FDG whole-body positron emulsion tomography (18F-FDG PET) has become an established imaging modality for a variety of cancers. Today, 18F-FDG PET is utilized to differentiate benign from malignant non-functioning adrenal masses. In this report, a 25-year-old woman presented with a 2-month history of left flank pain. Abdominal CT revealed a left 6.5 x 4.5 cm adrenal mass with regular margins and focal calcification. To make a differential diagnosis, 18F-FDG PET was performed. Preoperative laboratory studies showed that the mass was non-functioning. A left adrenalectomy was performed through a left subcostal incision. The final pathologic evaluation revealed adrenal oncocytoma. We present the disassociation between preoperative 18F-FDG PET and pathologic findings of a benign adrenocortical oncocytoma.

131I labeling of tamoxifen and biodistribution studies in rats.

Tamoxifen [TAM ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine)] has been used as an antiestrogen drug for treatment and prevention of human breast cancer. Tamoxifen was labeled with 131I using iodogen as an oxidizing agent. Mass spectroscopy of the cold standard showed that the labeling occurs in ortho position to the phenyl ether position of TAM as expected. Quality control, radiochemical yield and stability were established using the radioelectrophoresis method. The radiolabeled compound maintained its stability throughout working period of 24 h. Scintigraphic imaging was performed and tissue distribution was determined in Albino Wistar rats. According to biodistribution and imaging experiments the radiolabeled compound presented estrogen receptor (ER) specificity and it was uptaken by endometrium as well as breast tissue.

Regulation of the transient outward K(+) current by Ca(2+)/calmodulin-dependent protein kinases II in human atrial myocytes.

Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) have important functions in regulating cardiac excitability and contractility. In the present study, we examined whether CaMKII regulated the transient outward K(+) current (I(to)) in whole-cell patch-clamped human atrial myocytes. We found that a specific CaMKII inhibitor, KN-93 (20 micromol/L), but not its inactive analog, KN-92, accelerated the inactivation of I(to) (tau(fast): 66.9+/-4.4 versus 43.0+/-4.4 ms, n=35; P<0.0001) and inhibited its maintained component (at +60 mV, 4.9+/-0.4 versus 2.8+/-0.4 pA/pF, n = 35; P<0. 0001), leading to an increase in the extent of its inactivation. Similar effects were observed by dialyzing cells with a peptide corresponding to CaMKII residues 281 to 309 or with autocamtide-2-related inhibitory peptide and by external application of the calmodulin inhibitor calmidazolium, which also suppressed the effects of KN-93. Furthermore, the phosphatase inhibitor okadaic acid (500 nmol/L) slowed I(to) inactivation, increased I(sus), and inhibited the effects of KN-93. Changes in [Ca(2+)](i) by dialyzing cells with approximately 30 nmol/L Ca(2+) or by using the fast Ca(2+) buffer BAPTA had opposite effects on I(to). In BAPTA-loaded myocytes, I(to) was less sensitive to KN-93. In myocytes from patients in chronic atrial fibrillation, characterized by a prominent I(sus), KN-93 still increased the extent of inactivation of I(to). Western blot analysis of atrial samples showed that delta-CaMKII expression was enhanced during chronic atrial fibrillation. In conclusion, CaMKII control the extent of inactivation of I(to) in human atrial myocytes, a process that could contribute to I(to) alterations observed during chronic atrial fibrillation.

[Annuloplasty reduces the mitral leaflets mobility]. / L'annuloplastie réduit la mobilité des deux feuillets mitraux.

The posterior mitral leaflet is usually motionless following mitral valve repair. The aim of this study was to assess (1) the geometric changes of the left ventricular base following prosthetic ring annuloplasty and (2) their impact on the anterior mitral leaflet (AML) mobility. Thirty five patients operated upon for mitral valve repair underwent an intraoperative transesophageal echographic study before and after annuloplasty. A posterior leaflet resection was achieved in 29 cases and ring annuloplasty alone in 6 cases. No repair technique was performed on the AML. Four parameters were assessed: the anteroposterior mitral annulus diameter, the aortomitral angle, the opening and closure angles of the AML. Annuloplasty resulted in a drastic reduction of the mitral annulus from 36.8 +/- 5.6 mm to 20.9 +/- 3.8 mm (systole, long axis view) (p < 0.0001). The aortomitral angle decreased following annuloplasty from 115.1 +/- 8.3 to 108.0 +/- 9.60 (systole, long axis view) (p < 0.0001). No difference was observed between systolic and diastolic measurments concerning the mitral annulus or the aortomitral angle. The opening angle of the AML remained unchanged whereas the closure angle increased from 17.8 +/- 6.10 to 26.6 +/- 6.70 (long axis view) (p = 0.0001) resulting in a displacement of the coaptation point towards the apex. Consequently, the excursion of the anterior leaflet throughout the cardiac cycle decreased following annuloplasty from 43 +/- 130 to 32.5 +/- 11 (long axis view) (p < 0.0001).

Studies of controlled reperfusion after ischemia. XIX. Reperfusate composition: benefits of blood cardioplegia over fluosol DA cardioplegia during regional reperfusion--importance of including blood components in the initial reperfusate.

HYPOTHESIS: Initial reoxygenation with blood cardioplegic solution produces better regional recovery than with Fluosol DA cardioplegic solution (Green Cross Corporation, Osaka, Japan) because blood cardioplegia ensures delivery of important blood components (i.e., plasma and red blood cells) that limit reperfusion damage. METHODS: Twenty-five dogs underwent 2 hours of ligation of the left anterior descending coronary artery followed by controlled reperfusion at 50 mm Hg through an internal mammary graft on total vented bypass. Five dogs received normal blood reperfusion, 10 dogs received a 20-minute reperfusion with Fluosol DA 20% cardioplegic solution, and 10 others received a blood cardioplegic reperfusate of identical composition (i.e., pH, calcium, potassium, glucose, osmolarity). Regional oxygen consumption was measured during reperfusion, and segmental shortening (ultrasonic crystals), tissue water content, and histochemical damage (triphenyltetrazolium chloride stain) were assessed 2 hours later. RESULTS: Reperfusion with normal blood failed to restore contractile function (3% systolic shortening), caused severe edema (81% water content), and caused marked histochemical damage (48% triphenyltetrazolium chloride nonstaining). Hearts reperfused with Fluosol DA cardioplegic solution did not take up as much oxygen as hearts receiving blood cardioplegic reperfusion (37 versus 54 ml/100 gm, p less than 0.05). Blood cardioplegia was superior to Fluosol DA cardioplegia in recovery of segmental contractility (69% versus 34% systolic shortening, p less than 0.05), produced less edema (79.5% versus 80.9% water content, p less than 0.05), and produced less histochemical damage with triphenyltetrazolium chloride (11% versus 40% area of nonstaining/area at risk, p less than 0.05). CONCLUSIONS: Initial reperfusion with a blood cardioplegic solution ensures better oxygen utilization, superior recovery of regional contractility, and less tissue damage than Fluosol DA cardioplegic reperfusion. These data emphasize the importance of including blood components (plasma or red blood cells) in the oxygenated cardioplegic reperfusate to limit reperfusion injury.

Studies of controlled reperfusion after ischemia. XX. Reperfusate composition: detrimental effects of initial asanguineous cardioplegic washout after acute coronary occlusion.

UNLABELLED: This study tests whether initial asanguineous washout of potentially toxic substances that accumulate during ischemia improves recovery produced by blood cardioplegic reperfusion and evaluates the role of plasma versus whole blood cardioplegia. METHODS: Twenty-four dogs underwent 2 hours of occlusion of the left anterior descending coronary artery and 20 minutes of blood cardioplegic reperfusion on total vented bypass. In 13 dogs, a 5-minute infusion of either a crystalloid (n = 7) or plasma (n = 6) cardioplegic solution (containing the same pH, calcium potassium, and osmolarity as blood cardioplegia) was given immediately before reoxygenation with blood cardioplegia. Regional oxygen uptake and coronary vascular resistance were measured during controlled reperfusion, and segmental shortening (ultrasonic crystals), tissue water content, and histochemical damage (triphenyltetrazolium chloride stain) were assessed 1 hour after bypass was discontinued. RESULTS: Asanguineous cardioplegic washout before reoxygenation with blood cardioplegic solution resulted in a progressive (+42%) increase in coronary vascular resistances (from 123 to 176 units, p less than 0.05) and low oxygen utilization during 20 minutes of blood cardioplegic reperfusion (29 ml/100 gm, p less than 0.05); coronary vascular resistance remained low throughout blood cardioplegic reperfusion without washout (from 109 to 98 units), and oxygen utilization was 54 ml/100 gm (p less than 0.05). Neither plasma nor crystalloid washout restored substantial regional systolic shortening (3% systolic shortening versus 73% systolic shortening with blood cardioplegia), and asanguineous washout caused more myocardial edema (81.1% +/- 80.9% versus 79.5% water content, p less than 0.05) and produced extensive transmural triphenyltetrazolium chloride damage (48% +/- 41% versus 8% nonstaining in area at risk, p less than 0.05) than initial blood cardioplegic reperfusion. CONCLUSION: Asanguineous cardioplegic washout before blood cardioplegic reperfusion limits oxygen utilization during subsequent controlled reperfusion, restricts early recovery of systolic shortening, allows more myocardial edema, and produces extensive histochemical damage, which may be avoided by initial reoxygenation with blood cardioplegia. The red blood cells appear more important than the plasma components of blood cardioplegia.

Studies of controlled reperfusion after ischemia. XVII. Reperfusion conditions: controlled reperfusion through an internal mammary artery graft--a new technique emphasizing fixed pressure versus fixed flow.

UNLABELLED: This study tests the usefulness of delivering a controlled reperfusate through an internal mammary graft after acute ischemia by applying a percutaneous technique of mammary artery cannulation and compares reperfusion at fixed pressure versus fixed flow. METHODS: Twenty-one dogs underwent 2 hours of ligation of the left anterior descending coronary artery followed by regional controlled revascularization on total vented bypass. A reperfusion catheter was introduced percutaneously from the brachial artery into the internal mammary artery. Five dogs received normal blood reperfusion at 50 mm Hg pressure, and eight dogs received a regional blood cardioplegic reperfusate at 50 mm Hg before reperfusion with normal blood. Eight additional dogs received regional cardioplegia at 30 ml/min for 20 minutes. Coronary vascular resistance, segmental shortening (ultrasonic crystals), tissue water content, and histochemical damage (triphenyltetrazolium chloride stain) were assessed. RESULTS: Reperfusion with normal blood increased coronary vascular resistance progressively to 62% above initial values (p less than 0.05) and failed to restore regional contractility (9% +/- 6% systolic shortening, p less than 0.05). In contrast, coronary resistance remained low throughout blood cardioplegic reperfusion at fixed pressure and the reperfused muscle recovered immediate contractility (73% systolic shortening, p less than 0.05). Controlled reperfusion at a fixed flow rate resulted in pressure that ranged from 30 to 80 mm Hg, slightly less recovery of systolic shortening (57%), and less return of contractile reserve (81% versus 114%, p less than 0.05). Regional blood cardioplegic reperfusion limited edema formation (79.5 versus 82% water content, p less than 0.05) and histochemical damage (11% versus 50% area of necrosis/area at risk, p less than 0.05). CONCLUSION: An internal mammary artery graft can be used effectively in the setting of acute ischemia if a controlled blood cardioplegic reperfusate is delivered through it to ensure limitation of histochemical damage, low reflow phenomenon, and restoration of immediate segmental contractility. Controlled-pressure reperfusion seems superior to fixed-flow reperfusion. A technique is described that may allow preoperative insertion of the reperfusion catheter in the internal mammary artery in the catheterization laboratory.

Studies of controlled reperfusion after ischemia. XVIII. Reperfusion conditions: attenuation of the regional ischemic effect by temporary total vented bypass before controlled reperfusion.

This study tests the hypothesis that total vented bypass can attenuate the regional ischemic effect during a defined time interval before controlled blood cardioplegic reperfusion. Thirty-three dogs underwent 2 or 4 hours of occlusion of the left anterior descending coronary artery and then received a regional blood cardioplegic reperfusate on total vented bypass. Cardiopulmonary bypass and reperfusion were started after 2 hours of ischemia in eight dogs, and after 4 hours of ischemia in 25 others. Among the 25 dogs, seven had total vented bypass started after the first 2 hours of the 4 hours of regional ischemia. Segmental shortening (ultrasonic crystals), tissue water content (wet/dry weight), and histochemical damage (triphenyltetrazolium chloride stain) were assessed 2 hours after reperfusion. Dogs reperfused after 2 hours of ischemia recovered 73% +/- 8% of control systolic shortening and sustained only 11% triphenyltetrazolium chloride nonstaining. Dogs undergoing 4 hours of regional ischemia, but with total vented bypass 2 hours before reperfusion had improved recovery of systolic shortening (49% versus 31%, p less than 0.05), limited epicardial edema (79.6% versus 81.1% water content, p less than 0.05), and reduced histochemical damage (24% versus 39% triphenyltetrazolium chloride nonstaining, p less than 0.05). These findings imply that institution of total vented bypass during ischemia attenuates the infarct process, increases regional recovery of contractility, limits edema and restricts histochemical damage, and may be a useful adjunct to myocardial salvage when controlled reperfusion can be provided.

Studies of retrograde cardioplegia. II. Advantages of antegrade/retrograde cardioplegia to optimize distribution in jeopardized myocardium.

This study tests the hypothesis that retrograde/antegrade cardioplegic delivery can overcome the limitations of poor cardioplegic distribution resulting from either technique alone and, potentially, may expand the safety of using internal mammary artery grafts in cardiac muscle in jeopardy of inadequate cardioplegic protection. Jeopardized myocardium was produced in 20 dogs by ligating the left anterior descending coronary artery for 15 minutes before starting cardiopulmonary bypass and by 1 hour of aortic clamping with multidose 6 degrees C cold blood cardioplegia. Five dogs received antegrade cardioplegia via the aortic root. Ten dogs received retrograde cardioplegia via the coronary sinus. Five additional dogs received retrograde/antegrade cardioplegia via both routes. The ligature on the left anterior descending coronary artery was removed after aortic unclamping, and regional myocardial temperature (thermistor probe), segmental shortening (ultrasonic crystals), and global left ventricular and right ventricular myocardial function were evaluated. Antegrade cardioplegia produced excellent right ventricular cooling (14 degrees C) and allowed complete right ventricular functional recovery. However, it failed to cool muscle supplied by the left anterior descending coronary artery (only 31 degrees versus 12 degrees C, p less than 0.05), postischemic global left ventricular function recovered only 38% (p less than 0.05), and segmental shortening in the region supplied by the left anterior descending coronary artery recovered only 22% (p less than 0.05). Retrograde cardioplegia produced homogeneous cooling (17 degrees C) and allowed near normal recovery of global and regional left ventricular function (99% and 86%), but right ventricular cooling was variable (19 degrees to 30 degrees C) and right ventricular function recovered inconstantly (range 64% to 100%, average 82%). The best myocardial protection occurred after retrograde/antegrade cardioplegia; myocardial cooling was homogeneous, left ventricular and right ventricular global function recovered completely (95% and 90%), and regional contractility in muscle supplied by the left anterior descending coronary artery returned to 84% of control. We conclude that retrograde/antegrade cardioplegia provides better myocardial protection than either technique alone, ensures good cardioplegic distribution to the left and right ventricles, and allows regional delivery of cardioplegic flow to segments supplied by occluded arteries.(ABSTRACT TRUNCATED AT 400 WORDS)

Studies of controlled reperfusion after ischemia. XXI. Reperfusate composition: superiority of blood cardioplegia over crystalloid cardioplegia in limiting reperfusion damage--importance of endogenous oxygen free radical scavengers in red blood cells.

UNLABELLED: Postischemic damage is caused partially by oxygen free radical-mediated injury. This study will show that (1) crystalloid cardioplegia with room air oxygen is deleterious because it is devoid of free radical scavengers and (2) blood cardioplegia limits damage because it contains endogenous free radical scavengers in red blood cells. METHODS: Thirty-two dogs underwent 2 hours of ligation of the left anterior descending coronary artery followed by 20 minutes of regional blood cardioplegic reperfusion on bypass. Ten dogs received only the blood cardioplegic solution (containing its endogenous free radical scavengers); five received initial blood cardioplegia (5 minutes) with endogenous free radical scavengers (catalase and glutathione peroxidase) blocked by aminotriazole and N-ethylmaleimide, respectively; 12 received initial crystalloid cardioplegic solution oxygenated by room air (oxygen tension = 150 mm Hg); seven without and five with exogenous free radical scavengers (superoxide dismutase, catalase, coenzyme Q10); five received initial deoxygenated crystalloid cardioplegic solution (oxygen tension = 6 mm Hg); and five received deoxygenated crystalloid cardioplegic solution. RESULTS: Blood cardioplegia with endogenous free radical scavengers produced the best recovery of systolic shortening (69% systolic shortening) and resulted in the least histochemical damage (11% triphenyltetrazolium chloride nonstaining). The worst recovery and most damage occurred if blood cardioplegia was preceded by oxygenated crystalloid cardioplegia (3% systolic shortening, 48% triphenyltetrazolium chloride nonstaining; p less than 0.05 versus blood cardioplegia) or if free radical scavengers were blocked in the initial period of blood cardioplegia (3% systolic shortening, 41% triphenyltetrazolium chloride nonstaining; p less than 0.05 versus blood cardioplegia). Conversely, deoxygenation or supplementation of oxygenated crystalloid cardioplegic solution with exogenous free radical scavengers restored 60% systolic shortening (p less than 0.05 versus oxygenated crystalloid cardioplegia) and 54% systolic shortening (p less than 0.05 versus oxygenated crystalloid cardioplegia) and reduced damage to 34% and 21% (both p less than 0.05 versus oxygenated crystalloid cardioplegia). CONCLUSION: Blood cardioplegic solutions containing their own endogenous free radical scavengers are superior to crystalloid cardioplegic solutions, because they limit oxygen-mediated perfusion damage and restore contractile function. Initial crystalloid cardioplegic washout negates the salutary effect of blood cardioplegia. Exogenous free radical scavenger supplementation or deoxygenation of the cardioplegic reperfusate is necessary only if crystalloid cardioplegia is used.

Studies of controlled reperfusion after ischemia. XXII. Reperfusate composition: effects of leukocyte depletion of blood and blood cardioplegic reperfusates after acute coronary occlusion.

OBJECTIVES: This study evaluates the role of leukocyte depletion during initial reoxygenation with normal blood and blood cardioplegic reperfusates in limiting reperfusion damage. METHODS: Twenty-eight dogs underwent 2 hours of ligation of the left anterior descending coronary artery. The initial reperfusate (37 degrees C) was delivered on total vented bypass to the left anterior descending artery by a calibrated pump via an internal mammary artery graft at 50 mm Hg for 20 minutes. Eight dogs received normal (normokalemic, nonenriched) blood reperfusion (leukocyte count 8000/mm3) and six were reperfused with leukocyte-depleted normal blood (leukocyte count less than 100/mm3). Of 14 dogs reperfused with substrate-enriched (hyperkalemic) blood cardioplegic solution, six received a cardioplegic solution with a leukocyte count less than 100/mm3. RESULTS: Leukocyte depletion of normal blood reduced reperfusion-induced arrhythmias from 63% to 17% (p less than 0.05). Coronary vascular resistance at initial reperfusion was low and remained low during substrate-enriched blood cardioplegic reperfusion with both normal and reduced leukocyte counts. In contrast, coronary vascular resistance rose 63% with normal blood reperfusion, and this increase was avoided by leukocyte depletion (2.6 versus 4.0 mm Hg x ml/min, p less than 0.05). Coronary vascular resistance after 20 minutes was, however, higher than that with blood cardioplegia with normal or decreased leukocyte counts. Negligible functional recovery followed reperfusion with normal blood and leukocyte-depleted blood (12% and 6% of control systolic shortening). In contrast, substantial segmental recovery followed blood cardioplegic reperfusion (73% systolic shortening, p less than 0.05) but was not improved by leukopheresis (81% systolic shortening). Leukocyte depletion of normal blood reperfusate reduced histochemical damage from 53% to 38% (p less than 0.05), but the least histochemical damage followed blood cardioplegic reperfusion with a normal or reduced leukocyte count (8% or 11%, p less than 0.05). CONCLUSIONS: These findings suggest an important role for leukocytes in reperfusion damage, but reperfusate leukocyte filtration alone is inferior to blood cardioplegic reperfusion. Leukocyte depletion of blood cardioplegic solutions seems unnecessary after only 2 hours of ischemia.

Studies of controlled reperfusion after ischemia. XXIII. Deleterious effects of simulated thrombolysis preceding simulated coronary artery bypass grafting with controlled blood cardioplegic reperfusion.

This study tests whether simulated thrombolysis before controlled reperfusion (i.e., simulated coronary artery bypass) causes reperfusion injury that obviates the benefits of subsequent controlled reperfusion and results in unnecessary ventricular arrhythmias. Fifteen dogs underwent acute occlusion of the left anterior descending coronary artery. In 10 dogs we simulated thrombolysis after 1 hour of ischemia (delivering 10% to 15% of control flow at 5 ml/min), followed 1 hour later by either normal blood reperfusion at systemic pressure (to simulate percutaneous transluminal coronary angioplasty) in five dogs or regionally controlled blood cardioplegic reperfusion on bypass in five others to simulate coronary bypass. In five dogs ischemia was prolonged to 2 hours, and the initial reperfusate was blood cardioplegic solution on total vented bypass (to simulate primary coronary bypass). All hearts receiving simulated thrombolysis (100%) after 1 hour of ischemia had reperfusion-induced ventricular fibrillation. All hearts treated by simulated angioplasty recovered regional contractility (56% of control systolic shortening), whereas there was no (0%) recovery of spontaneous contractility after subsequent blood cardioplegic reperfusion, and only two (40%) dogs had contractile reserve capacity (6% +/- 49%). Conversely, surgically controlled blood cardioplegic reperfusion without preceding low-flow normal blood reperfusion after 2 hours of ischemia resulted in no ventricular arrhythmias (0%; p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis), 72% +/- 7% (p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis) recovery of regional contractility (ultrasonic crystals), and 114% +/- 11% (p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis) recovery of contractile reserve with calcium chloride stimulation. We conclude that controlled reperfusion (simulating coronary artery bypass) with blood cardioplegic solution produces immediate functional recovery and avoids the ventricular fibrillation that follows simulated thrombolysis despite the need for prolonged ischemic time. Preceding controlled reperfusion by normal blood reperfusion (simulated thrombolysis) shortens the ischemic time but nullifies immediate functional recovery possible by simulated coronary bypass and produces unnecessary arrhythmias.

Reperfusate composition: benefits of marked hypocalcemia and diltiazem on regional recovery.

This study tests the hypothesis that improved muscle salvage is possible by markedly reducing the ionic calcium (Ca++) of the reperfusate (less than 250 mumol/L) and adding a calcium channel-blocking drug (diltiazem). Preliminary pilot studies showed that a 20-minute infusion of markedly hypocalcemic substrate-enriched blood cardioplegic solution (less than 250 mumol/L Ca++) did not affect left ventricular function adversely and that a 150 to 250 mumol/L substrate-enriched blood cardioplegic solution, delivered during total vented bypass with diltiazem, 300 micrograms/kg body weight, produced the most consistent functional recovery and the least histochemical evidence of damage (triphenyltetrazolium chloride nonstaining) after 2 hours of regional ischemia. Experimental studies of 2 hours of regional ischemia were followed by either regional normocalcemic (1000 to 1200 mumol/L) blood cardioplegic reperfusion in bypassed hearts, with or without diltiazem, or hypocalcemic (150 to 150 mumol/L) blood cardioplegic reperfusion with diltiazem for 20 minutes. Results showed that hypocalcemic blood cardioplegic solution with diltiazem produced superior recovery of systolic shortening (58% versus 11% systolic shortening, p less than 0.05) and limitation of histochemical damage (11% versus 54%, p less than 0.05), in comparison with normocalcemic blood cardioplegic solution without diltiazem. These studies suggest that modifying the regional reperfusate by markedly reducing ionic calcium levels and adding calcium channel-blocking drugs is safe and may improve myocardial salvage more than using substrate-enriched blood cardioplegic solution alone.

Studies of retrograde cardioplegia. I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries.

This study defines the nutritive (i.e., capillary) distribution of blood cardioplegic solutions delivered via retrograde and antegrade techniques to muscle supplied by open and occluded coronary arteries where myocardial segments are in jeopardy of inadequate cardioplegic protection. Open-chest anesthetized dogs were studied by mixing radioactive microspheres (15 +/- 5 microns) with a blood cardioplegic solution and administering cardioplegia either into the coronary sinus or into the proximal aorta with the left anterior descending coronary artery open or occluded (30% +/- 2% area at risk). Nutritive flow (i.e., percentage of delivered 15 microns microspheres trapped in myocardial capillaries) during retrograde infusions averaged 65% versus 87% with antegrade cardioplegia (p less than 0.05). Retrograde and antegrade cardioplegic nutritive flow to all left ventricular regions was comparable with the left anterior descending coronary artery open (65 versus 82 ml/100 gm/min, p greater than 0.05), and both methods provided preferential hyperperfusion of subendocardial muscle (endocardial/epicardial ratios 1.6 and 1.5, respectively). Nutritive flow to muscle supplied by the occluded left anterior descending coronary artery was preserved better by retrograde than antegrade cardioplegia (35 versus 5 ml/100 gm/min, p less than 0.05). Preferential subendocardial hyperperfusion was maintained during retrograde cardioplegia (52 ml/100 gm/min, endocardial/epicardial ratio 1.6), but flow was redistributed away from subendocardial muscle with antegrade cardioplegia (less than 2 ml/100 gm/min, endocardial/epicardial, 0.29, p less than 0.05). Left ventricular flow was reduced markedly during retrograde infusion with the left anterior descending coronary artery open or occluded (23 and 12 ml/100 gm/min), but septal cooling was superior to antegrade cardioplegia (15 degrees +/- 1 degree C versus 20% +/- 3%, p less than 0.05) despite near-normal antegrade septal flow (the left anterior descending coronary artery was ligated beyond the first septal branch). Right ventricular nutritive flow was only 7 ml/100 gm/min during retrograde coronary sinus perfusion and was maintained normally with antegrade cardioplegia.(ABSTRACT TRUNCATED AT 400 WORDS)

Superiority of controlled surgical reperfusion versus percutaneous transluminal coronary angioplasty in acute coronary occlusion.

Although percutaneous transluminal coronary angioplasty is successful in more than 90% of patients after acute coronary occlusion, overall mortality remains approximately 10% with higher subgroup mortality (i.e., occlusion of the left anterior descending coronary artery, multivessel disease, age older than 70 years, cardiogenic shock) and early recovery of regional wall motion is marginal. This multicenter report shows that controlled surgical reperfusion in patients with acute coronary occlusion reduces overall and subgroup mortality and restores substantial early contractility. In a survey from six institutions, 156 consecutive patients with acute coronary occlusion documented by angiography underwent surgical revascularization with controlled reperfusion using amino acid-enriched blood cardioplegic solution on total vented bypass. Ventricular wall motion was studied by echocardiography or multiple gated acquisition scan on postoperative days 5 to 7 and scored independently (0 = normal, 1 = mild hypokinesia, 2 = severe hypokinesia, 3 = akinesia, 4 = dyskinesia). Results are compared with results in 1203 patients with acute coronary occlusion treated by angioplasty in five reported medical series. Surgically treated patients were revascularized at longer ischemic intervals (6.3 versus 3.9 hours, p < 0.05) and had a greater incidence of left anterior descending occlusion (61% versus 43%, p < 0.05), multivessel disease (42% versus 22%, p < 0.05), and cardiogenic shock (41% versus 10%, p < 0.05), with 12 patients undergoing cardiopulmonary resuscitation en route to the operating room. Surgical results were superior in all categories, with overall mortality reduced from 8.7% after angioplasty to 3.9% after coronary bypass (p < 0.05). All surgical deaths occurred in patients with preoperative cardiogenic shock. Regional wall motion recovered significantly (score < 2) in 131 of 150 (87%) surgically treated patients with an average score of 0.9 +/- 0.8 (normal to mild hypokinesia) despite longer ischemic times.

Homograft replacement of the mitral valve. Graft selection, technique of implantation, and results in forty-three patients.

UNLABELLED: Because of experience gained in reconstructive mitral valve surgery, we have reevaluated the implantation of cryopreserved homografts in the mitral position. Forty-three patients, aged 11 to 69 years (mean 34 years), underwent mitral valve replacement with cryopreserved mitral homografts. The indications for the procedure were acute endocarditis (n = 14), rheumatic stenosis (n = 26), systemic lupus endocarditis (n = 2), and marasmic endocarditis (n = 1). All homografts were obtained from hearts explanted in the course of transplantation and were cryopreserved at -160 degrees C in 10% dimethyl sulfoxide solution without antibiotics. Appropriate sizing was based on morphologic study of the homografts and preoperative echocardiographic assessment of the recipient valve. In 82 homografts analyzed, the height of the anterior leaflet was 25 +/- 3 mm and the distance from the anulus to the apex of the anterior papillary muscle was 21 +/- 3 mm. The morphologic features of the papillary muscles were classified according to four types of increasing complexity. Nine valves with complex (type IV) papillary muscle abnormalities were discarded. Echocardiographic measurements of the valve were matched with those of the homograft identification cards and a slightly larger homograft was selected (measurements + 3 mm). Partial homograft replacement was done in case of a localized lesion (abscess or calcification) (n = 21). Total homograft replacement was undertaken in the presence of diffuse lesions (n = 22). Two hospital deaths occurred as a result of poor cardiac output. One patient required reoperation on the tenth postoperative day after a dehiscence on the valvular suture line. After a mean follow-up of 14 months, there has been one late death caused by a bronchial neoplasm and one reoperation for residual stenosis (partial replacement). The remaining patients were in either New York Heart Association class I (n = 25) or II (n = 13). Thirty-three patients were in sinus rhythm. Follow-up echocardiography has revealed no mitral regurgitation (n = 20), minimal mitral regurgitation (n = 13), and mild mitral regurgitation (n = 5). Surface valve area has been calculated at 2.5 +/- 0.4 cm2 in partial homograft reconstruction and 2.7 +/- 0.3 cm2 in total homograft replacement, with a transvalvular gradient of 3 +/- 4 mm Hg. CONCLUSION: In a selected group of patients, the use of mitral homografts significantly extended the present limitations of reparative surgery of the mitral valve.

Studies on prolonged acute regional ischemia. V. Metabolic support of remote myocardium during left ventricular power failure.

This study tests the hypothesis that metabolic support of remote "nonischemic" myocardium during acute infarction will reverse the trend toward cardiogenic shock. Thirty-seven dogs underwent ligation of the left anterior descending coronary artery and 50% stenosis of the circumflex coronary artery. Irreversible ventricular fibrillation developed in 11 of them. The 26 survivors were observed for up to 6 hours; global and regional left ventricular function (cardiac index, stroke work index, ultrasonic crystals) and regional blood flow (radioactive microspheres) were measured. After 2 hours, eight dogs received an intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, coenzyme Q10, and 2-mercapto-propionyl-glycine for 4 hours. Five dogs received the mannitol infusion to raise serum osmolarity 30 mOsm. Four additional dogs received the intravenous substrate infusions over 4 hours without undergoing ischemia. The substrate infusion for 4 hours caused no change in regional or global cardiac function in the four control dogs. Three of nine untreated dogs died of cardiogenic shock, and progressive left ventricular power failure occurred in the six others (40% decrease in cardiac index, 50% decrease in stroke work index, p less than 0.05) because of persistent dyskinesia in the left anterior descending region (-40% of systolic shortening, p less than 0.05) and hypocontractility in the circumflex region (48% of control systolic shortening, p less than 0.05), despite normal transmural blood flow in the posterior left ventricular wall (76 ml/100 gm/min). In contrast, in treated dogs, hypercontractility recovered in the circumflex segment (138% of systolic shortening) and stroke work index rose to control levels (91%) without a change in regional blood flow. Mannitol infusion did not improve hemodynamics or avoid the development of progressive left ventricular power failure. We conclude that cardiogenic shock after myocardial infarction is due, in large part, to impaired ability of "nonischemic" myocardium to maintain hypercontractility. This limitation can be prevented by metabolic support of viable muscle, and the data imply that intravenous substrate infusions may be helpful before definitive treatment (i.e., coronary artery bypass grafting) is undertaken.

Dynamic cardiomyoplasty at seven years.

Since January 1985, the date of the first dynamic cardiomyoplasty, until April 1992, 52 patients with end-stage heart disease were operated on in our institution. Mean preoperative New York Heart Association functional class was 3.3 and ventricular ejection fraction 16% +/- 3%. Associated procedures in 23 patients comprised ventricular aneurysm resection (10), valve surgery (9), coronary artery bypass (8), and tumor resection (3). Thirty-eight patients had a ventricular reinforcement, 13 a ventricular substitution, and 1 an atrial reinforcement using the left latissimus dorsi muscle. Preassist mortality rate before full latissimus dorsi muscle stimulation was 7 of 13 patients (54%) in the 1985 to 1987 period and 5 of 39 (12%) in the 1988 to 1992 period. The causes of death were heart failure (4), multiorgan failure (4), septicemia (2), ventricular fibrillation (1), and sudden death (1). Multivariate analysis of factors influencing hospital mortality showed that age, cardiac suture technique, associated surgical procedures, biventricular heart failure, and hemodynamic instability plus inotropic drug support were predictors of unfavorable outcome. All patients were followed up for from 2 months to 7 years (mean 21 months). Postassist mortality rate was 8 of 40 (20%). Causes of death included heart failure (5), ventricular fibrillation (1), myocardial infarction (1), and gastric bleeding (1). Preoperative risk factors influencing long-term mortality were permanent New York Heart Association functional class IV, biventricular heart failure, atrial fibrillation, cardiothoracic ratio greater than 60%, and ejection fraction less than 15%. Actuarial survival at 7 years was 70.4% (preassist mortality excluded). Surviving patients were in a mean New York Heart Association functional class of 1.8 (preoperatively 3.3, p < 0.05). The average ejection fractions (rest/stress) were 25%/28% at 1 year, 26%/30% at 2 years, and 23%/28% at 3 years. Average cardiothoracic ratios were 57% +/- 3% at 1 year, 56% +/- 2% at 2 years, and 57% +/- 2.5% at 3 years. Catheterization obtained in 20 patients showed no significant changes at rest in capillary wedge pressure, pulmonary artery pressure, and diastolic left ventricular pressure when compared with preoperative pressures. Average ejection fractions increased from 24% to 30.6%. Maximal oxygen consumption increased from 12.8 +/- 3.5 to 18.6 +/- 4 ml/min per kilogram. The number of rehospitalizations resulting from congestive heart failure was reduced to 0.4 hospitalizations per patient per year (preoperatively 2.4, p < 0.05). In 62% of the patients, pharmacologic therapy was diminished after the operation. Three patients required orthotopic heart transplantation 6 months, 4 years, and 5 years after cardiomyoplasty.

Studies on prolonged acute regional ischemia. I. Evidence for preserved cellular viability after 6 hours of coronary occlusion.

Six hours of coronary occlusion has been thought to produce extensive and irreversible transmural damage and no possibility of salvage by reperfusion. This has been based on findings of adenosine triphosphate depletion and histochemical (triphenyltetrazolium chloride nonstaining) and ultrastructural changes (conventional preparatory techniques). This study tests the hypothesis that, in contrast to conventional wisdom, considerable structural and mitochondrial functional integrity remains in cardiac muscle subjected to 6 hours of regional ischemia. Twenty open-chest anesthetized dogs underwent isolation of the left anterior descending coronary artery and were observed for 6 hours. Eight of the 20 did not undergo ischemia and served as controls. Twelve underwent 6 hours of proximal ligation of the left anterior descending coronary artery (30% +/- 2% area at risk). Transmural biopsy specimens were analyzed. Coronary occlusion reduced regional blood flow (radioactive microspheres) to less than 10 ml/100 gm/min (p less than 0.05) and dyskinesia persisted in the area at risk for 6 hours. High-energy phosphates (adenosine triphosphate and creatine phosphate) declined to negligible levels and histochemical damage occurred (49% +/- 12% triphenyltetrazolium chloride non-staining). Mitochondrial ultrastructural changes (low protein denaturation embedding technique) were mild (the integrity of the inner and outer mitochondrial surface membranes and crystal membranes was maintained and myofibrillar degeneration did not occur). Mitochondrial oxidative phosphorylation rate remained at 63% of control levels, respiratory control index remained at 77%, and adenosine diphosphate/oxygen ratio was maintained at 96%. Mitochondrial Ca++ increased with lanthanum (from 26 to 46 nmol/mg protein, p less than 0.05), but irreversible calcium precipitation did not occur; calcium could be mobilized to normal levels (i.e., 13 nmol/mg protein) by ethylenediaminetetraacetic acid chelation. These data support our inference that necrosis does not occur after 6 hours of coronary occlusion and suggest that muscle salvage by reperfusion is possible after at least 6 hours of regional myocardial ischemia.