C1-INH and its effect on infarct size and ventricular function in an acute pig model of infarction, cardiopulmonary bypass, and reperfusion.

BACKGROUND: Recent studies suggest that complement inhibition reduces reperfusion injury. A clinical setting with local application of a C1 esterase inhibitor (C1-INH) has been modeled in an animal study in order to further investigate these findings. METHODS: In 21 pigs, the left anterior descending coronary artery (LAD) was occluded distally to the first diagonal branch for 2 hours (h), including 1 h of cardioplegic arrest during CPB. After release of the coronary snare, C1-INH or NaCl (control) was applied to the aortic root. Thereafter, the aortic cross-clamp was removed and the heart was reperfused for 30 minutes before weaning from CPB. Left ventricular pressure volume analysis was performed by a multielectrode conductance catheter and the area at risk and infarct size were determined from excised hearts. RESULTS: The following data were observed (mean+/-SEM) for the control group and the C1-INH group, respectively, after 1-h ligation of the LAD: heart rate (HR) 86+/-3 and 93+/-6 beats/min, stroke volume (SV) 1.2+/-0.1 and 1.2+/-0.1 ml/kg, aortic pressure (AoP) 83+/-6 and 87+/-5 mmHg, left ventricular end-diastolic pressure (LVedP) 12+/-1 and 11+/-2 mmHg; two hours after weaning from CPB: HR 106+/-9 and 123+/-4 beats/min, SV 0.9+/-0.1 and 0.9+/-0.1 ml/kg, AoP 65+/-5 and 79+/-7 mmHg, LVedP 9+/-1 and 8+/-1 mmHg. Conductance catheter measurements showed no improved left ventricular performance after C1-INH application. Infarct size to area at risk ratio was 61.5+/-4.2% for controls and 61.4+/-4.8% for C1-INH. CONCLUSIONS: Intracoronary application of complement inhibitor in an acute infarction model, which mimicked a clinical setting of urgent coronary bypass grafting after ischemia, has been shown to neither influence the area of infarction, nor the ventricular function.

Capillary leak syndrome after cardiopulmonary bypass in elective, uncomplicated coronary artery bypass grafting operations: does it exist?

OBJECTIVE: Operations coupled with cardiopulmonary bypass may provoke a systemic inflammatory response, and it has been suggested that this responses causes capillary leakage of proteins, edema formation, and even organ failure. However, capillary leak syndrome is mainly a clinical diagnosis and has not been verified as yet by actual demonstration of protein leakage from the circulation. We have therefore measured the disappearance of labeled plasma protein before and after cardiopulmonary bypass. METHODS: Sixteen patients scheduled for elective coronary artery bypass grafting were enrolled in a prospective controlled study. The cardiopulmonary bypass circuit was primed with crystalloids only. Tumor necrosis factor alpha, interleukin 6, interleukin 8, anaphylatoxin C3a, and terminal complement complex C5b9 levels were determined before, during, and 3 hours after cardiopulmonary bypass. The transvascular escape rate of plasma protein from the intravascular compartment was assessed by measuring the disappearance of intravenously injected Evans blue dye before and during the third hour after cardiopulmonary bypass. RESULTS: A significant inflammatory response could be demonstrated by means of the 5 measured mediators after bypass. The maximal increase, as compared with the baseline value, was found for interleukin 6 (36-fold). The transvascular escape rate of Evans blue dye was similar before and after bypass (7.6 +/- 0.6%/h vs 7.3 +/- 0.6%/h). CONCLUSIONS: The above data confirm the systemic inflammatory response induced by cardiopulmonary bypass. Contrary to expectations, the transvascular escape rate of Evans blue dye did not change when comparing values before and after bypass. The data do not support the concept of increased protein leakage in the exchange vessels after bypass. We were unable to demonstrate a capillary leak syndrome.

Does a hyperoncotic cardiopulmonary bypass prime affect extravascular lung water and cardiopulmonary function in patients undergoing coronary artery bypass surgery?

OBJECTIVE: Different types of colloidal priming for cardiopulmonary bypass (CPB) have been used to reduce fluid load and to avoid the fall of plasma colloid osmotic pressure (COP) that leads to edema formation and consequently can cause organ dysfunction. The discussion about the optimal priming composition, however, is still controversial. We investigated the effect of a hyperoncotic CPB-prime with hydroxyethyl starch (HES) 10% (200;0.5) on extravascular lung water (EVLW) and post-pump cardiac and pulmonary functions. METHODS: In 20 randomized patients undergoing elective coronary artery bypass graft surgery (CABG), a colloid prime (COP: 48 mmHg, HES-group, n = 10) and a crystalloid prime (Ringer's lactate, crystalloid group, n = 10) of equal volume were compared with respect to the effects on cardiopulmonary function. Cardiac index (CI), mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance index (SVRI), pulmonary artery pressure (PAP), pulmonary vascular resistance index (PVRI), alveolo-arterial oxygen difference (AaDO(2)), pulmonary shunt fraction (Q(s)/Q(T)), EVLW (double-indicator dilution technique with ice-cold indocyanine green), COP, fluid balance and body weight were evaluated peri-operatively. RESULTS: Pre-operative demographic and clinical data, CPB-time, cross-clamp time and the number of anastomoses were comparable for both groups. During CPB, COP was reduced by 20% in the HES-group (18.9 +/- 3.7 vs. 23.7 +/- 2.2 mmHg, P < 0.05) while it was reduced by more than 50% of the pre-CPB value (9.8 +/- 2.0 vs. 21.4 +/- 2.1 mmHg, P < 0.05) in the crystalloid group (P < 0.05 HES- vs. crystalloid group). Post-CPB EVLW was unchanged in the HES-group but it was elevated by 22% in the crystalloid group (P < 0.05 HES- vs. crystalloid group), CI was higher in the HES-group (3.4 +/- 0.3 vs. 2.7 +/- 0.5l/min, P < 0.05). Fluid balance was less in the HES-group (813 +/- 619 vs. 2143 +/- 538, P < 0.05). Post-operative weight gain could be prevented in the HES-group but not in the crystalloid group (1.5 +/- 1.2 vs. -0.3 +/- 1.5, P < 0.05). No significant differences were seen for MAP, PAP, PCWP, SVRI, PVRI, AaDO(2) and (Q(s)/Q(T)) between the two groups at any time. CONCLUSIONS: Hyperoncotic CPB-prime using HES 10% improves CI and prevents EVLW accumulation in the early post-pump period, while pulmonary function is unchanged. This effect can be of benefit especially in patients with congestive heart failure.

Pulmonary function after biventricular bypass for autologous lung oxygenation.

OBJECTIVE: Biventricular bypass (BVB) with autologous lung perfusion is an attractive concept to ameliorate systemic inflammatory response by eliminating the oxygenator from the extracorporeal circulation. The effect of biventricular bypass as compared to heart-lung bypass (HLB) on pulmonary function parameters was therefore studied in an experimental model. METHODS: Heart-lung bypass using a membrane oxygenator or biventricular bypass using the autologous lung for gas exchange was performed for 120 min in an alternating series of 12 mongrel dogs with the heart arrested for 90 min by crystalloid cardioplegia and 30 min reperfusion, followed by a 120 min observation period. Systemic (CO, SVR) and pulmonary hemodynamics (PVR), extravascular lung water (EVLW, double indicator), gas exchange (FiO(2), PaO(2), PaCO(2)), lung compliance (PC), and ventilation (RMV) at FiO(2)=0.5 required to maintain PaCO(2) at 40 mmHg, were measured. Blood cell counts (Leuco, Thrombo) were performed. RESULTS: All animals were weaned from extracorporeal circulation without inotropes, no differences were observed in cardiac output and blood pressures. The following data were obtained in % change from pre-bypass values 60 min after extracorporeal circulation (*:P<0.05, HLB vs. BVB): PVR, +108 vs. +45*; EVLW, +21 vs. -2*; PC, -12 vs. +4*; PaO(2), -8 vs. +21; RMV, +21 vs. +2*; Leuco, -65 vs. -12*; Thrombo, -62 vs. -35*. CONCLUSION: During and after heart-lung bypass the lung is subject to severe ischemia-reperfusion injury as indicated by edema, cell trapping, and impaired gas exchange. The data demonstrate superior preservation of pulmonary mechanics and function after biventricular bypass as compared to heart-lung bypass and support the clinical strategy of using biventricular bypass in patients with impaired lung function.

Effect on coronary artery flow reserve and resistance in the remote area after acute coronary artery occlusion in the pig model.

BACKGROUND: It has been reported that vasodilator function in remote myocardial regions supplied by "angiographically normal" coronary arteries is impaired in patients after acute myocardial infarction (MI). The aim of this study was to determine whether coronary artery flow reserve and coronary artery resistance in remote, nonischemic areas are also altered in experimental MI. METHODS: Experiments were performed in anesthetized pigs. In group 1 infarction was induced by ligation of the left-anterior descending artery (LAD); group 2 consisted of sham-operated animals. Hemodynamic parameters, coronary artery resistance, and myocardial blood flow (MBF) were measured before and 4 hours after MI under rest and during infusion of adenosine. RESULTS: Coronary artery dilation by adenosine caused a similar increase in MBF before and 4 hours after coronary artery occlusion. Resting MBF after acute MI was not altered, although a significant reduction (15%; P < .04) in mean aortic pressure was observed compared with baseline. Coronary artery resistance was significantly reduced by adenosine (P < .04) before MI, as well as at 4 hours after MI (P < .03). Coronary artery flow reserve was not adversely affected. The sham-operated animals showed similar results without any significant differences between the two study groups. CONCLUSION: This study indicates that an acute MI in pigs did not increase coronary artery resistance in the remote area after MI and therefore did not adversely affect coronary artery flow reserve in the nonischemic vascular bed. Further studies are necessary to fully understand the exact mechanism of the alterations in remote flow reserve of patients after MI.

Influence of combined zero-balanced and modified ultrafiltration on the systemic inflammatory response during coronary artery bypass grafting.

OBJECTIVE: To evaluate whether combined zero-balanced and modified ultrafiltration affects the systemic inflammatory response in coronary artery bypass graft (CABG) patients. DESIGN: Randomized and controlled. SETTING: University-affiliated heart center. PARTICIPANTS: Forty-three patients scheduled for elective CABG. INTERVENTIONS: In the ultrafiltration group (UF group; n = 21), zero-balanced ultrafiltration was performed during rewarming and modified ultrafiltration immediately after the end of cardiopulmonary bypass (CPB). A control group of patients (n = 22) was treated identically to the treatment group except no ultrafiltration process was performed. MEASUREMENTS AND MAIN RESULTS: Immediately after CPB (ie, after zero-balanced ultrafiltration), and again after the modified ultrafiltration, the concentrations of interleukin-6 and interleukin-8 were significantly less (p < 0.05) in the UF group compared with the control group. Both proinflammatory cytokine levels peaked at 2 and 4 hours after CPB, at which time no difference between the two groups could be observed. The levels of measured anti-inflammatory mediators (interleukin-10 and interleukin-1 receptor antagonist) did not show any difference between the two groups. Intrapulmonary shunt fraction decreased in the course of the modified ultrafiltration from 31% +/- 1.2% to 25% +/- 1.3% (p < 0.01), whereas mean arterial pressure increased (69 +/- 1.8 to 80 +/- 2.8 mmHg; p < 0.01); neither parameter changed in the control group. Time to extubation was shorter in the UF group (6.1 +/- 0.5 v 8.6 +/- 0.7 hours; p < 0.05). CONCLUSION: It was concluded that the use of ultrafiltration diminished inflammatory response in a very limited time period immediately after CPB and, probably as a consequence, slightly improved clinical parameters.

Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures?

OBJECTIVE: To discover the possible effects of methylprednisolone on the systemic inflammatory response during aprotinin treatment. DESIGN: Randomized, double-blinded study. SETTING: University-affiliated heart center. PARTICIPANTS: Fifty-two patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: In the methylprednisolone group (n = 26), 1 g of methylprednisolone was administered 30 minutes before cardiopulmonary bypass (CPB). The 26 control patients received a placebo instead. High-dose aprotinin was administered to all participants. MEASUREMENTS AND MAIN RESULTS: After CPB, the concentration of the proinflammatory cytokines, interleukin-6 and interleukin-8, was significantly less in the methylprednisolone group. The anti-inflammatory interleukin-10 concentration was, in contrast, greater. After CPB, PaO2 was greater in the methylprednisolone group (245+/-17 v 195+/-16 mmHg). Dynamic pulmonary compliance was also greater, whereas the alveolar-arterial oxygen difference was less (376+/-17 v 428+/-16 mmHg). On arrival in the intensive care unit, the oxygen delivery index was greater in the methylprednisolone group (62+/-2.7 v 54+/-2.3 mL/min/m2) and the oxygen extraction rate was less (25%+/-0.02% v 30%+/-0.02%). After CPB, the cardiac index was significantly greater in the methylprednisolone group (4.1+/-0.2 v 3.6+/-0.2 L/min/m2). These patients had less blood loss postoperatively (616+/-52 v 833+/-71 mL; p = 0.017) and a greater urine output (8,015+/-542 v 6,417+/-423 mL/24 h; p = 0.024). CONCLUSION: The use of methylprednisolone attenuates the systemic inflammatory response during aprotinin treatment and improves clinical outcome parameters.

Effect of dopamine and atrial pacing on stunned myocardium.

OBJECTIVE: Post-ischaemic stunned myocardium shows an impaired function at restored coronary blood flow, but performance can be normalized by positive inotropic stimulation. The power of stunned myocardium, however, is not augmented with increasing heart rate by atrial pacing, which is in contrast to intact areas. This pathological response is mitigated by inhibiting the degradation of cyclic AMP. The present experiments studied the effect of stimulating cyclic AMP formation by dopamine on the response of stunned myocardium to atrial pacing. METHODS: In anaesthetized (piritramide) open chest pigs, heart rate, left ventricular and aortic pressure, left descending (LAD) and circumflex (LCX) coronary artery and aortic blood flow, myocardial systolic shortening in the LAD and LCX area were monitored, and myocardial power was calculated. The LAD region was subjected to ischaemia and reperfused for 2 h. Subsequently, heart rate was raised by right atrial pacing before and during intravenous infusion of dopamine (10 microg/kg per min). The ischaemic/reperfused area was sliced post mortem and stained by triphenyl tetrazolium chloride to exclude myocardial infarction. Data from 11 experiments are presented. RESULTS: After 2 h LAD reperfusion, LAD blood flow and power were 100% and 36% of pre-ischaemic control, respectively, indicating myocardial stunning. The power of the intact area was not changed significantly (111% of control). Increasing heart rate by +36 and +70 from 94 beats/min increased the power of the intact area to 161% and 183% of control; the power of the stunned myocardium decreased to 34% and 19% of pre-stunning control. Dopamine increased the power of the stunned region to 143% of the pre-stunning level and the power of the intact area to 206% of control. Increasing heart rate by +34 and +70 from 113 beats/min during dopamine, increased the power of the intact myocardium to 288% and 344% of control and the power of the stunned region to 177% and 174% of the pre-stunning level. CONCLUSIONS: The data confirm the pathological response of stunned myocardium to atrial pacing and the recruitment of a functional reserve by catecholamines. The adverse effect of pacing on the function of stunned myocardium is abolished by positive inotropic stimulation. Possibly, the cyclic AMP system is involved in the normal response to pacing and this pathway is disturbed in stunned myocardium; other defects are not excluded or supported, however. Physiologically increased heart rate by an increased activity of the sympathetic nervous system, is probably not accompanied by a reduced power of stunned myocardium, due to the associated positive inotropic stimulation.

Effect of milrinone and atrial pacing on stunned myocardium.

OBJECTIVE: Most mammalian cardiac muscles show a positive force-frequency relation, which is turned into a negative relation in failing hearts. Stunned myocardium shows similar defects as failing myocardium, it has a functional reserve recruitable by positive inotropic interventions, and possibly shows a disturbed response to increased heart rate. The present experiments compare in vivo the response of stunned and intact myocardium to atrial pacing before and during inotropic stimulation by milrinone. METHODS: In anaesthetised (piritramide) open chest pigs, heart rate, left ventricular and aortic pressure, left descending (LAD) and circumflex (LCX) coronary artery and aortic blood flow, myocardial systolic shortening in the LAD and LCX area were monitored, and myocardial power was calculated. The LAD region was subjected to ischaemia and reperfused. Heart rate was raised by right atrial pacing after 90 min reperfusion before and during i.v. milrinone (105 microg/kg bolus + 8 microg/kg per min infusion). The ischaemic/reperfused area was sliced post mortem and stained by triphenyl tetrazolium chloride to exclude myocardial infarction. Data from ten experiments are presented. RESULTS: After 90 min LAD reperfusion, LAD blood flow and power were 110 and 36% of preischaemic control, respectively, indicating myocardial stunning. The power of the intact area was not changed (102% of control). Pacing from 87 to 164 per min increased the power of the intact area (+96%), the power of the stunned myocardium decreased (-64%). Milrinone increased the power of the stunned region to 72% of the pre-stunning level and the power of the intact area by +51%. Pacing from 111 to 164 per min during milrinone increased the power of the intact myocardium to the same level as before milrinone, the power of the stunned region did not change. CONCLUSIONS: Stunned myocardium responds pathologically to atrial pacing with a negative staircase in contrast to the positive staircase of intact myocardium. Inotropic stimulation by the phosphodiesterase inhibitor milrinone recruited the functional reserve of stunned myocardium. Milrinone did not restore a positive staircase in stunned myocardium, but power was maintained during atrial pacing. The pathological staircase of stunned myocardium may arise from an impaired availability of cyclic AMP, but the data do not exclude defects in calcium handling, a dysfunction of the sarcoplasmic reticulum, or an impaired Ca-sensitivity of the myofilaments.

[Experimental principles for preserving annulo-ventricular integrity of the mitral valve]. / Experimentelle Grundlagen zur Erhaltung der anuloventrikulären Integrität der Mitralklappe.

Despite numerous improvement in cardiac surgery the results in mitral valve replacement are still not satisfactory, since impaired left ventricular function continues to be a problem during the postoperative course. In order to investigate the effect of mitral valve replacement on left ventricular function canine experiments were performed: During extracorporeal circulation bileaflet mitral valve prostheses were implanted preserving the ventriculo-annular continuity. Flexible wires were slung around the chordae of the subvalvular mitral apparatus and brought to the outside through the left ventricular wall. Left ventricular diameters were measured by sonomicrometry, left ventricular stroke volume, left ventricular enddiastolic volume and ejection fraction by dye dilution technique as well as left ventricular and aortic pressure by catheter tip manometers. After finishing cardiopulmonary bypass control values were registered and different preload values achieved by volume loading with blood transfusions to left ventricular enddiastolic pressures of 12 mm Hg. Subsequently under normovolumic conditions the chordae tendineae of the anterior and posterior papillary muscles of the mitral valve were cut from the outside, while the heart was beating, by application of electrocautery on the steel wires. Following severance of the ventriculo-annular continuity of the mitral valve again function curves of left ventricular hemodynamics were made during volume transfusions. When the chordae had been divided the left ventricular enddiastolic diameter increased by 10% in the major axis, while in the minor axis no significant changes occurred. The systolic shortening was impaired substantially by reduction of 43% during the ejection phase when the subvalvular mitral apparatus had been severed. Left ventricular enddiastolic volume was increased by 18% at any preload level, while left ventricular ejection fraction was reduced by 16%. Consequently left ventricular stroke volume was decreased by 24% at any left ventricular enddiastolic volume, when the chordae had been divided. It can be concluded that left ventricular geometry is changed when the annulo-ventricular continuity has been interrupted at mitral valve replacement: The major axis of the left ventricle is increased and the enddiastolic volume is augmented. The left ventricle is only able to eject the same stroke volume at higher preload levels when the chordae tendineae have been divided. The same cardiac performance can only be achieved by volume loading and at the expense of higher wall tension, which leads to unfavorable conditions in terms of cardiac muscle mechanics with reduced exercise tolerance. These data speak for preservation of the annulo-ventricular continuity in mitral valve replacement. Provided that these results from acute canine experiments can be transferred to humans, one would suggest that preservation of the mitral subvalvular apparatus is of importance in patients with dilated hearts and with impaired left ventricular function.

Determination of phenylmercapturic acid in urine of benzene-exposed BDF-1 mice.

This paper describes a procedure for the identification of phenylmercapturic acid in urine of benzene-exposed mice. Collected urine of benzene exposed mice was adjusted to pH 7 and applied to an anion exchanger. After extraction with diethyl ether and evaporation to dryness, the sample was dissolved in aqueous phosphoric acid and injected into the HPLC. HPLC conditions included an ODS column and an eluent consisting of tetrabutylammoniumhydrogensulfate-methanol (75:25, v/v), the absorbance wavelength was 255 nm. The detection limit of phenylmercapturic acid was 3 mg/l in mouse urine.

Determination of benzene metabolites in urine of mice by solid-phase extraction and high-performance liquid chromatography.

A method was developed for quantitative measurement of trans,trans-muconic acid, catechol, hydroquinone and phenol in urine. Hydrolysis of esterified and glucuronized phenolic compounds was effected by specific enzymes. The hydrolysed mixture was purified and separated by solid-phase extraction with an anion exchanger, followed by extraction with diethyl ether. By using a clean-up procedure the natural background from mouse urine could be reduced, so that the detection limit of the metabolites was in the range 3-60 mg/l. Optimization of the chromatographic conditions resulted in a short high-performance liquid chromatography analysis time. Phenol had the longest retention time of about 10 min. The clean-up procedure could also be used for phenylmercapturic acid, an additional benzene metabolite, but for sensitive high-performance liquid chromatographic detection of phenylmercapturic acid other conditions are necessary.

Importance of the mitral apparatus for left ventricular function: an experimental approach.

In an experimental study of 31 anesthetized dogs the importance of the mitral apparatus for the left ventricular function was investigated. During extracorporeal circulation bileaflet mitral valve prostheses were implanted preserving the mitral subvalvular apparatus. Flexible wires were slung around the chordae tendineae and exteriorized through the left ventricular wall to cut the chordae by electrocautery from the outside when the heart was beating again. External and internal left ventricular dimensions were measured by sonomicrometry, left ventricular stroke volume by electromagnetic flowmeters around the ascending aorta, left ventricular end-diastolic volume by dye dilution technique, and left ventricular pressure by catheter tip manometers. Different preload levels were achieved by volume loading with blood transfusion before and after cutting the chordae tendineae. When the chordae had been divided peak systolic left ventricular pressure did not change. Heart rate only increased at the lowest left ventricular end-diastolic pressures of 3-4 mmHg, but remained unchanged at higher preload levels. Cardiac output decreased significantly up to -9% at left ventricular end-diastolic pressures of 5-10 mmHg, while left ventricular dp/dtmax showed a consistent reduction of up to -15% at any preload level. Significant reductions were also seen in systolic shortening in the left ventricular major axis (by external measurements -27%, by internal recording -43%). Left ventricular end-diastolic dimensions increased in the major axis by +2% when recorded externally, by +10% when measured internally. Systolic and diastolic changes in the minor axis were not consistent and different in the external and internal recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the serotonin-antagonist ketanserin on the function of ischaemic and normally perfused myocardium and modification by beta-1-blockade in anaesthetized normotensive dogs.

The 5-HT-2 antagonist ketanserin (KAS) has been successfully used to treat acute hypertension in coronary bypass surgery. The present study was performed to investigate the effect of KAS on ischaemic myocardium. In 11 anaesthetized (piritramide) dogs, systolic contraction (sdL) and end-diastolic length (edL) of myocardium supplied by the left descending coronary artery (LAD) and the left circumflex coronary artery (LCX) were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular dP/dtmax and end-diastolic pressure (LVedP), heart rate (HR), stroke volume, and LAD flow (QLAD). Regional ischaemia to decrease sdLLAD (-48%) was achieved by LAD stenosis (QLAD -47%). Concomitantly, edLLAD increased by 8%. However, the other variables did not change. Then KAS was given i.v. (0.15 + 0.15 + 0.30 + 0.6 mg/kg) at 15-min intervals. Following KAS, prestenotic sdLLAD recovered in a dose-dependent manner. LVedP and edLLAD decreased, sdLLCX increased, and the other variables were not affected. This functional recovery of ischaemic myocardium was attenuated by pretreatment with metoprolol (MET, 1 mg/kg) prior to LAD stenosis. The ischaemic area was not irreversibly damaged, however, as proven by the recovery of prestenotic sdLLAD values after release of the stenosis. The improved systolic shortening of ischaemic myocardium following KAS did not result from restored QLAD due to post-stenotic vasodilation or break up of platelet aggregates (QLAD did not increase) or from reduced afterload (AoP did not decrease). Obviously, it was mediated by beta-1-receptors, as shown by the attenuation of the beneficial effect of KAS by pretreatment with MET.

Action of benzene metabolites on murine hematopoietic colony-forming cells in vitro.

Five benzene metabolites--phenol, catechol, hydroquinone, parabenzoquinone, and trans,trans-muconaldehyde--were tested in vitro in murine hematopoietic cell cultures for erythrocytic (BFU-E and CFU-E) and granulocytic (CFU-C) colony growth. The dose range was 4 x 10(-4) to 4 x 10(-8) M. Of these compounds, phenol showed the lowest toxicity. In general, CFU-E cultures were far more sensitive than CFU-C and BFU-E. The results are discussed in relation to the test system used, the in vivo sensitivity of CFU-E, and the lack of knowledge about in vivo concentrations of these compounds.

Global and regional ventricular function following intracoronary application of papaverine.

Intracoronary injection of papaverine is used to determine coronary flow reserve in patients. The present study was to investigate the effect of papaverine on the performance of myocardium with reduced flow reserve. In nine anaesthetized open-chest dogs a bypass from the aorta to the left circumflex coronary artery (LCX) was established. Left ventricular end-diastolic and aortic pressure, dP/dt, stroke volume, LCX blood flow, and ECG were monitored. The performance of a segment of subendocardial wall supplied by the LCX was assessed by sonomicrometry. Peak reactive hyperaemia after 15s bypass occlusion was 1.44 +/- 0.09 times the baseline flow (41 ml/min), indicating reduced coronary flow reserve. Papaverine was injected into the bypass (0.3, 0.6, 1.2, 2.5, 5.0 mg/ml, 1 ml in 15s). The maximum LCX flow following PAPA 0.3 mg was comparable to peak reactive hyperaemia, but 10-15% higher after injection of 0.6-5.0 mg papaverine. Systolic shortening of the myocardium (control: 17.5% of end-diastolic length) became reduced in a dose-dependent fashion (5-25%) for about 1 min following papaverine injection. Stroke volume (control: 0.94 +/- 0.12 ml/kg) was reduced by about 8%, left ventricular end-diastolic pressure (control: 6.2 +/- 0.8 mmHg) increased by 15%, and dP/dtmin (control: 1850 +/- 150 mmHg/s) was curtailed by 15-25%. The ECG showed a transient T inversion and S-T depression following papaverine administration and in one experiment ventricular fibrillation occurred after the injection of 2.5 mg papaverine. The observed effects of intracoronary papaverine are consistent with the theory of transient subendocardial ischaemia arising from a redistribution of blood flow from the subendocardial to the subepicardial layers, because of greater vasodilatory capacity in the latter than in the former.

Preservation versus severance of the subvalvular apparatus in mitral valve replacement: an experimental study.

Preservation of the subvalvular apparatus in mitral valve replacement has been suggested to improve postoperative left ventricular performance. As it is difficult to quantify the change in left ventricular performance clinically, an experimental model was devised to demonstrate the contribution of the subvalvular apparatus to left ventricular function. In eight dogs mitral valve replacement (St. Jude prostheses) was performed, preserving the subvalvular apparatus by plicating the leaflets with the prosthesis on the mitral annulus. Left ventricular function was assessed during volume loading with blood before and after cutting the chordae tendineae by means of electrocautery applied via flexible wires slung around the chordae and exteriorized through the left ventricular wall. Left ventricular internal diameters were measured by sonomicrometry. End-diastolic volume (LVedV) and stroke volume were determined by dye dilution and left ventricular pressure (LVP) by cathter tip manometer. The results showed that after cutting the chordae the heart rate did not differ from the pre-cut values at any LVedP. The peak left ventricular pressure was only significantly reduced at an LVedP of 5 mmHg and minor axis diameters were only increased at an LVedP of 9-12 mmHg. Significant changes were observed, however, in LV dP/dtmax (= maximum rise of LVP) (-15%), major axis end-diastolic diameter (+10%) and systolic shortening (-40%), end-diastolic volume (+18%) and ejection fraction (-16%) at any LVedP, and stroke volume (-24%) at any LVedV.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Nd: YAG laser coagulation of myocardium on coronary vessels.

Laser coagulation of arrhythmogenic myocardium proved to be an effective surgical therapy for refractory arrhythmias. To determine the influence of Nd: YAG laser coagulation of myocardium on coronary vessels, a total of 48 transcatheter laser impacts (10 W, 10 sec, 7 W mm2) were directed to the left ventricular free wall via endocardial (24 lesions in 2 dogs) or epicardial (24 lesions in 2 dogs) approach. In 8 of 24 endomyocardial lesions (2 and 6 months old) coronary vessels with a diameter of greater than 50 microns were found within the coagulation zones. The volume of these lesions was significantly (P less than 0.01) smaller (139 +/- 43 mm3) than those (n = 16) with coronary vessels measuring less than 50 microns (311 +/- 87 mm3). Volumes of epimyocardial lesions (1-2 hours old) produced by transcoronary irradiation with normal coronary blood flow were significantly (P less than 0.01) smaller (31 +/- 17 mm3) than with reduced (73 +/- 22) or interrupted (119 +/- 34 mm3) blood flow (n = 8, each). Both directly irradiated coronary vessels and those found within the coagulation zones and scars appeared histologically normal through all layers with an intact intima without fibrosis or thrombosis. The ultrastructure of irradiated arteries, even with total interruption of blood flow, was no different from that of non-irradiated controls. Thus, coronary artery blood flow significantly reduces the volume of coagulated myocardium, whereas the vessels themselves appear to remain undamaged by laser irradiation as used for myocardial coagulation.

Ribose intervention in the cardiac pentose phosphate pathway is not species-specific.

Ribose is cardioprotective in the rat in a variety of pathophysiological conditions. The metabolic basis for this effect is the low capacity of the oxidative pentose phosphate pathway in the myocardium. Ribose bypasses this pathway, elevates the available pool of 5-phosphoribosyl-l-pyrophosphate, and thus stimulates the biosynthesis of adenine nucleotides. In this study reported here the activity of glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the oxidative pentose phosphate shunt, was very low in the human heart and was of the same order of magnitude in the myocardium of various animal species. Furthermore, ribose had a similar stimulating effect on myocardial adenine nucleotide biosynthesis in the guinea pig, in which hemodynamic parameters are different from those in the rat. It is concluded that the metabolic basis for the effectiveness of ribose is similar in all species investigated.