Microbial relatives of the seed storage proteins of higher plants: conservation of structure and diversification of function during evolution of the cupin superfamily.

This review summarizes the recent discovery of the cupin superfamily (from the Latin term "cupa," a small barrel) of functionally diverse proteins that initially were limited to several higher plant proteins such as seed storage proteins, germin (an oxalate oxidase), germin-like proteins, and auxin-binding protein. Knowledge of the three-dimensional structure of two vicilins, seed proteins with a characteristic beta-barrel core, led to the identification of a small number of conserved residues and thence to the discovery of several microbial proteins which share these key amino acids. In particular, there is a highly conserved pattern of two histidine-containing motifs with a varied intermotif spacing. This cupin signature is found as a central component of many microbial proteins including certain types of phosphomannose isomerase, polyketide synthase, epimerase, and dioxygenase. In addition, the signature has been identified within the N-terminal effector domain in a subgroup of bacterial AraC transcription factors. As well as these single-domain cupins, this survey has identified other classes of two-domain bicupins including bacterial gentisate 1, 2-dioxygenases and 1-hydroxy-2-naphthoate dioxygenases, fungal oxalate decarboxylases, and legume sucrose-binding proteins. Cupin evolution is discussed from the perspective of the structure-function relationships, using data from the genomes of several prokaryotes, especially Bacillus subtilis. Many of these functions involve aspects of sugar metabolism and cell wall synthesis and are concerned with responses to abiotic stress such as heat, desiccation, or starvation. Particular emphasis is also given to the oxalate-degrading enzymes from microbes, their biological significance, and their value in a range of medical and other applications.

Assessment of the efficacy of interventions to limit ischemic injury by direct measurement of intramural carbon dioxide tension after coronary artery occlusion in the dog.

Although numerous interventions have been shown to exert a salutary effect on the ischemic myocardium, the severity of ischemia generally has been measured by indirect techniques. In the present investigation the effect of ischemia on intramural carbon dioxide tension (PmCO(2)) was measured directly in the open-chest, anesthetized dog with a mass spectrometer during repetitive 10-min coronary artery occlusions separated by 45-min periods of reflow; simultaneously, regional myocardial blood flow in the ischemic area was measured by (127)Xenon washout. In all dogs the increase in PmCO(2) from before to 10 min after the first occlusion (DeltaPmCO(2)) exceeded that during subsequent occlusions. In those dogs not receiving an intervention (controls), DeltaPmCO(2) during the third occlusion was similar to that during the second occlusion. When propranolol, hyaluronidase, and nitroglycerin were administered to different groups of dogs before the third occlusion, each caused significantly smaller elevations in DeltaPmCO(2) than those occurring during the control second occlusion, and the combination of all three interventions induced the smallest increase in DeltaPmCO(2). Regional myocardial blood flow rose with hyaluronidase and was unchanged with propranolol, nitroglycerin, and the three drugs in combination. In contrast to these beneficial interventions, isoproterenol infused with the third occlusion caused a higher DeltaPmCO(2) than during the control second occlusion. It is concluded, first, that interventions that modify the severity of ischemia can be evaluated by measuring intramural carbon dioxide tension; second, that propranolol, hyaluronidase, and nitroglycerin reduce ischemic injury, whereas isoproterenol increases it; and third, that the combination of propranolol, hyaluronidase, and nitroglycerin exerts an additive beneficial effect on ischemia.

The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta-interactomes Improve Function Predictions.

The functions of roughly a third of all proteins in Streptococcus pneumoniae, a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions between evolutionarily conserved proteins in other bacteria. We found that such interactions significantly improved our ability to predict a protein's function, allowing us to provide functional predictions for 299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE Identification of protein interactions in bacterial species can help define the individual roles that proteins play in cellular pathways and pathogenesis. Very few protein interactions have been identified for the important human pathogen S. pneumoniae. We used an experimental approach to identify over 2,000 new protein interactions for S. pneumoniae, the most extensive interactome data for this bacterium to date. To predict protein function, we used our interactome data augmented with interactions from other closely related bacteria. The combination of the experimental data and meta-interactome data significantly improved the prediction results, allowing us to assign possible functions to a large number of poorly characterized proteins.

Intraaortic balloon counterpulsation as a temporary support measure in decompensated critical aortic stenosis.

Intraaortic balloon counterpulsation was instituted in two adult patients whose condition was rapidly deteriorating because of critical decompensated valvular aortic stenosis. The acute hemodynamic effect of counterpulsation in these patients was compared with the effect of counterpulsation in three control patients with unstable angina and no aortic valve disease. Augmentation of aortic diastolic pressure was similar in both groups; however, in contrast to the patients with unstable angina, the patients with aortic stenosis had no decrease in left ventricular systolic pressure. Counterpulsation resulted in an increase in the transvalvular pressure gradient, which was associated with a slight increase in stroke volume. In both patients with aortic stenosis, the institution of counterpulsation resulted in marked clinical improvement, which facilitated successful valve replacement surgery. The benefit from counterpulsation in critically decompensated aortic stenosis appears to be derived almost entirely from augmentation of the diastolic coronary filling gradient. The improvement that results from counterpulsation suggests that ischemia is the major cause of decompensation.

Pulmonary embolism after cardiac surgery.

OBJECTIVES: We examined the incidence of pulmonary embolism after cardiac surgery. BACKGROUND: Because venous thromboembolism is considered to be an uncommon complication after cardiac surgery, its incidence was documented in a consecutive series of 1,033 patients who underwent cardiac surgery over a 5-year period. METHODS: Parallel cohorts of patients in a tertiary referral center were evaluated and the incidence of pulmonary embolism was compared in subgroups of patients undergoing coronary bypass surgery, valve surgery and combined procedures. RESULTS: Pulmonary embolism developed in 33 (3.2%) of the 1,033 cardiac surgical patients, within 2 weeks of a coronary bypass operation in most; it did not develop in any patient who had isolated valve replacement surgery (p < 0.05). The diagnosis of pulmonary embolism was established by pulmonary angiography in 24 patients, ventilation/perfusion lung scan in 3, postmortem examination in 5 and clinical examination in 1 patient. Important risk factors for pulmonary embolism included prolonged postoperative recovery, obesity and hyperlipidemia. The mortality rate was 18.7% in patients with in contrast to 3.3% in those without pulmonary embolism (p < 0.01). CONCLUSIONS: Although pulmonary embolism is rare after isolated valve replacement, it is not an uncommon complication after coronary bypass surgery.

Hemodynamic effects of nitroglycerin in an experimental model of acute aortic regurgitation.

Afterload reduction is an accepted therapeutic modality for the treatment of congestive heart failure caused by chronic aortic regurgitation. However, the role of vasodilator therapy in acute aortic incompetence has not been established. To investigate this, left ventricular volume overload was produced in 18 dogs by constructing a valved conduit from the descending thoracic aorta to the left ventricular apex. The time course of aortic, pulmonary and conduit flows was analyzed in eight control studies and established stability of the experimental model. In the remaining 10 dogs, intravenous nitroglycerin, titrated to reduce mean aortic blood pressure by 40%, and placebo (ethanol) were each infused for 20 min periods. Compared with placebo, nitroglycerin significantly reduced aortic flow (3,945 +/- 324 to 3,397 +/- 362 ml/min, p less than 0.01), regurgitant flow (1,304 +/- 131 to 764 +/- 90 ml/min, p less than 0.001), septal-lateral end-diastolic diameter (47.5 +/- 1.8 to 46.5 +/- 1.8 mm, p less than 0.001), left ventricular end-diastolic pressure (6.9 +/- 0.8 to 6.0 +/- 0.6 mm Hg, p less than 0.05), left ventricular stroke work (19.0 +/- 2.6 to 10.8 +/- 1.7 g-m/beat, p less than 0.001) and systemic vascular resistance (2,253 +/- 173 to 1,433 +/- 117 dyne-s/cm5, p less than 0.001). In contrast, pulmonary flow, left anterior descending coronary flow and subendocardial pH did not change during infusion of either nitroglycerin or placebo. These data indicate that by decreasing preload and afterload, and by preserving coronary flow and tissue pH, nitroglycerin effectively reduced ventricular and regurgitant volumes in the setting of acute volume overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Six month postoperative hemodynamics of the Hancock heterograft and the Björk-Shiley prosthesis: results of a Veterans Administration cooperative prospective randomized trial.

In a Veterans Administration Cooperative Study involving 13 medical centers, 575 patients undergoing single valve replacement were prospectively randomized to receive either the standard Björk-Shiley prosthesis or the Hancock porcine heterograft (with a modified orifice for sizes 23 and smaller). The hemodynamic data in the 268 patients who underwent cardiac catheterization an average of 6 months (range 3 to 12) postoperatively are reported. Statistical analyses were performed on valve sizes 23, 25 and 27 in the aortic position, and 29, 31 and 33 in the mitral position. A wide variation was observed in mean pressure gradient and calculated orifice area in both valve types within all sizes in both the aortic and the mitral positions. In the aortic position, the Björk-Shiley prosthesis tended to have a lower pressure gradient and larger calculated orifice area than the Hancock heterograft, but the differences in gradient between the two valve types were significant only in the larger-sized valves. The difference in calculated area between the two valve types was not significant within each valve size. In the mitral position, there were no differences in gradient and calculated orifice area between the two types of prostheses. The postoperative cardiac index, regurgitant volume, pulmonary artery systolic and mean pressures, left ventricular end-diastolic pressure, left ventricular ejection fraction and left ventricular end-diastolic volume index did not differ in patients receiving the Björk-Shiley prosthesis from values in patients receiving the Hancock heterograft. Hence, the overall hemodynamic performance of both types of valves is remarkably similar. The choice between these two prostheses should, therefore, be governed not by the hemodynamic performance, but by other factors such as valve durability, risk of anticoagulation and incidence of valve-related complications.

Comparison of outcome after valve replacement with a bioprosthesis versus a mechanical prosthesis: initial 5 year results of a randomized trial.

The Veterans Administration Cooperative Study on Valvular Heart Disease was organized to compare survival and incidence of valve-related complications between patients receiving a bioprosthesis (the Hancock porcine heterograft) and a mechanical prosthesis (the Björk-Shiley spherical disc valve). Five hundred seventy-five patients undergoing single aortic or mitral valve replacement were randomized at surgery to one of the two valve types. At an average follow-up of 5 years (range 3 to 8) there are no statistically significant differences in survival between patients with the two valve types in the aortic valve replacement group. There is a statistically nonsignificant trend toward improved survival in patients undergoing mitral valve replacement with a bioprosthesis compared with a mechanical prosthesis (5 year survival probability was 0.70 +/- 0.05 and 0.58 +/- 0.06, respectively). Fatal and nonfatal valve-related complications occurred significantly less frequently in patients with a bioprosthesis compared with a mechanical prosthesis for both mitral and aortic valve replacement. Five year complication-free probability was 0.67 +/- 0.05 and 0.45 +/- 0.06, respectively, for patients with mitral valve replacement and 0.63 +/- 0.04 and 0.53 +/- 0.04, respectively, for those with aortic valve replacement. The difference in overall complication rates was largely due to the increased number of clinically significant but nonfatal bleeding episodes in patients receiving a mechanical prosthesis. Adjustment for differences in baseline characteristics between patients receiving a mitral mechanical prosthesis and a mitral bioprosthesis reduced the statistical significance of the difference in both mortality and complications.

Heterogeneity of heparin lots associated with thrombocytopenia and thromboembolism.

Thromboembolic complications may develop in patients with heparin-associated thrombocytopenia, presumably due to the formation of platelet aggregates. An unexpectedly high incidence of pulmonary embolism following coronary artery bypass surgery occurred during a brief period of time at a single institution, and all of these cases were found to be associated with thrombocytopenia. All patients tested during thrombocytopenia (five of five) had an increase in platelet-associated antibody. Serum samples from all five patients tested caused normal platelets to aggregate in vitro in the presence of one specific lot of beef lung heparin, which was in use in the operating room at the time; none of six other lots of beef lung heparin mediated in vitro platelet aggregation. Heparinase digestion of the heparin abolished the aggregating activity. It is concluded that thrombocytopenia and platelet activation caused by heparin may vary greatly even among different lots of heparin prepared from the same source.

Technetium-99m(Sn2+)pyrophosphate in ischemic and infarcted dog myocardium in early stages of acute coronary occlusion: histochemical and tissue-counting comparisons.

We have investigated the pattern of accumulation of Tc-99m(Sn2+)pyrophosphate (Tc-99m PPi) in myocardial tissue of dogs during the early stages of acute occlusion of the left anterior descending coronary artery. Three groups were studied after: (a) 40 min occlusion followed by 6 hr reperfusion (n = 6); (b) 6 hr occlusion followed by one hour reperfusion (n = 5); and (c) 7 hr occlusion with no reperfusion (n = 4). Areas of myocardial infarction were defined with triphenyl-tetrazolium chloride (TTC) staining, and blood flow was determined with 9-mu radioactive microspheres. In Group C uptake in infarcted and peri-infarct areas was not enhanced, most likely owing to low flow. In Group B, with late reperfusion, Tc-99m PPi sequestration was increased in both infarcted and peri-infarcted tissues. In Group A, areas ischemic during occlusion but with normal flow and viability by TTC after 6 hr of reperfusion showed significant uptake of Tc-99m PPi (twice the uptake of nonischemic regions).

Effects of bepridil on regional myocardial ischemia and comparison with verapamil.

This study was designed to assess the efficacy of bepridil in reducing regional myocardial ischemia and to compare its efficacy with that of verapamil. Forty-five anesthetized, open-chest dogs were subjected to three 5-minute occlusions of the left anterior descending coronary artery (LAD), each followed by 45 minutes of reperfusion. Eleven dogs (group 1) served as controls. In 10 dogs, bepridil, 5 mg/kg, was administered before the third occlusion (group 2). In 11 dogs, verapamil was administered before the third occlusion (group 3). In each dog, on-line intramyocardial hydrogen ion concentration and carbon dioxide tension were measured in the myocardial segment supplied by the LAD. Regional myocardial contractility was assessed in this area with 2 pairs of ultrasonic crystals inserted to determine percent segmental shortening. Regional myocardial blood flow was determined during each occlusion by washout of xenon-127. The increase in hydrogen ion concentration and carbon dioxide tension did not change from occlusion 2 to occlusion 3 in the control group. Both bepridil and verapamil elicited a significant reduction in the extent of regional ischemia, evidenced by a reduction in the accumulation of hydrogen ions, in occlusion 3 vs occlusion 2. Systolic bulging occurred during all occlusions and the periods of reperfusion were not sufficient to allow complete recovery of regional function. Bepridil and verapamil each caused a significant increase in percent segmental shortening (both p less than 0.025), and verapamil effected a significant improvement of function during occlusion 3 compared with occlusion 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative detection of regional left ventricular contraction abnormalities by 2-dimensional echocardiography. Comparison of myocardial thickening and thinning and endocardial motion in a canine model.

Myocardial infarction (MI) was produced in 27 dogs by ligation of the left anterior descending coronary artery. Two-dimensional (2-D) echocardiograms were performed through the closed chest before and serially after coronary ligation, in both the acute and healing stages of MI. Two-dimensional echocardiographic studies performed before the animals were killed were analyzed for left ventricular (LV) contraction defects by 2 algorithms--1 involving systolic myocardial thickening and thinning and the other by determining the extent of endocardial motion to derive cavity area shrinkage. Using the thickening algorithm, myocardial dysfunction was detected in 93% of the animals with MI; with the area shrinkage method, contraction abnormalities were detected in 96% of the animals with MI. When the heart was divided from base to apex into 3 short-axis sections, the thickening algorithm showed a trend toward better identification of normal regions than the area shrinkage algorithm. However, in predicting the circumferential extent of MI, the thickening-thinning method of analysis showed no advantage over the endocardial motion method (r = 0.77, standard error of the estimate = 0.16 versus r = 0.76, standard error of the estimate [SEE] = 0.16; p = not significant [NS]). These observations support the concept that either algorithm can be used effectively to detect the presence and quantify the circumferential extent of MI.

Efficacy of nadolol in preventing supraventricular tachycardia after coronary artery bypass grafting.

To investigate the efficacy of nadolol in the prevention of supraventricular arrhythmias after coronary artery bypass graft (CABG) surgery, 148 patients undergoing elective CABG were randomized in double-blind, placebo-controlled fashion to receive either nadolol or placebo. The test medication was started on the first postoperative morning and maintained as a single daily dose for 6 weeks. Aside from routine daily clinical evaluation and postoperative electrocardiographic monitoring, patients underwent 24-hour Holter recording once preoperatively and 3 times postoperatively. Seven patients were excluded from the evaluation of efficacy analysis because of insufficient postoperative data. There were no significant differences between the patients receiving nadolol (n = 67) and those receiving placebo (n = 74) with respect to age, preoperative heart rate, previous medications (including beta blockers), incidence of previous myocardial infarction, frequency of preoperative ventricular and supraventricular arrhythmias, concomitant valvular heart disease, mean cardiopulmonary bypass time, mean aortic cross-clamp time, use of blood and crystalloid cardioplegia, mean number of bypass grafts placed, postoperative use of inotropic agents and catecholamines and incidence of perioperative myocardial infarction. Analysis of postoperative Holter recordings showed that the heart rate was consistently and significantly higher in the placebo group throughout the period of the study (p less than 0.001). The average number of premature atrial contractions was significantly smaller in the nadolol group (p less than 0.05), and nadolol patients had fewer ventricular premature complexes, couplets and non-sustained ventricular tachycardias during the first week postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic features of an unruptured aneurysm of the right sinus of Valsalva.

A 2-cm aneurysm of the right sinus of Valsalva was documented in a patient with a prosthetic aortic valve. The M-mode findings differed from prior reports and mimicked those of aortic root dissection or a catheter placed in the right ventricular outflow tract. Two-dimensional echocardiograms readily distinguished the aneurysm of the right sinus of Valsalva from the alternative possibilities.

The effects of normothermic and hypothermic cardiopulmonary bypass on defibrillation energy requirements and transmyocardial impedance. Implications for implantable cardioverter-defibrillator implantation.

The influence of normothermic and hypothermic cardiopulmonary bypass on defibrillation energy requirements and transcardiac impedance is not well characterized. However, this relationship is of clinical importance during automatic defibrillator implantation done with concomitant cardiac surgery, and there is anecdotal information that criteria for successful implantation are harder to achieve after such operations. We studied the effect of controlled hypothermia on defibrillation energy requirements and transcardiac impedance in a canine model of cardiopulmonary bypass in which 26 animals underwent right atrial and femoral arterial cannulation, as well as continuous hemodynamic and intramyocardial temperature monitoring. The defibrillation energy requirements were evaluated at 60-minute intervals with an epicardial patch system, and transcardiac impedance was measured before and after the multiple inductions and terminations of ventricular fibrillation. In group 1 (n = 10) defibrillation energy requirements were evaluated immediately after initiation of cardiopulmonary bypass at 37 degrees C (T0), after gradual cooling to 28 degrees C (T1), and after rewarming to 37 degrees C (T2). Group 2 (n = 16) comprised time controls that were identically instrumented and studied, but maintained at 37 degrees C throughout. Percent successful defibrillation was plotted against delivered energy, and the raw data fit by logistic regression. The energy at which 50% of shocks were successful (E50) was 3.23 +/- 0.89 joules at T0, 5.12 +/- 1.85 joules at T1, and 4.42 +/- 1.22 joules at T2 in group 1; this was not significantly different from the corresponding group 2 E50 values, which were 3.11 +/- 1.39 joules, 4.95 +/- 2.47 joules, and 5.59 +/- 3.18 joules, respectively. Both groups demonstrated a significant increase in E50 during the first hour of cardiopulmonary bypass (mean increase from T0 to T1 was 1.89 joules in group 1 and 1.84 joules in group 2, p < 0.05). Transmyocardial impedance fell progressively during the group 2 experiments from 73.6 +/- 12.9 omega at the beginning of the T0 shock series to 61.4 +/- 8.9 omega at the end of the T2 shock series. A similar reduction in transmyocardial impedance was observed during the course of all the group 1 experiments; however, at the beginning of the T1 shock series impedance was significantly elevated to 77.4 +/- 12.3 omega (p < 0.05 compared with group 2 and with end T0 in group 1). There was no relationship between defibrillation energy requirements and transcardiac impedance; there was also no correlation between either of these parameters and intramyocardial extracellular pH or left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Significance of changes in resting left ventricular ejection fraction after coronary artery bypass grafting.

The prognostic significance of changes in resting left ventricular ejection fraction was examined in 102 patients who underwent successful coronary artery bypass grafting. Between preoperative and early postoperative radionuclide ventriculography, mean resting left ventricular ejection fraction improved from 47.2% to 53.9% (p less than 0.01). Left ventricular ejection fraction increased by 5% or greater in 64 patients (63%), remained unchanged (within 4%) in 31 (30%), and decreased by at least 5% in 7 (7%). During 14 to 39 months (mean 27 months) of clinical follow-up, patients with normal preoperative left ventricular ejection fraction had a lower prevalence of recurrent angina, congestive heart failure, and mortality resulting from cardiovascular disease. Cardiovascular morbidity and mortality occurred with equal frequency for patients who did and did not show early postoperative improvement in left ventricular ejection fraction (36% versus 39%). Among 69 patients who had a third radionuclide ventriculography at late follow-up, left ventricular ejection fraction was less than the early postoperative value in 69% and less than the preoperative result in 36%. Patients with early postoperative improvement in left ventricular ejection fraction were more likely to retain resting left ventricular contractile function, at least at the preoperative level (71% versus 46%).

Prognosis for aorta-coronary graft patency. A comparison of preoperative and intraoperative assessments.

For prognostication of aorta-coronary bypass graft patency, preoperative angiographic assessment of the recipient vessel and the regional left ventricle was compared with the intraoperative measurement of the internal diameter of the vessel and graft flow in 98 patients, in whom graft patency was evaluated at 1 year. Preoperative assessment of the recipient vessel did not correlate with the intraoperative measurement of the internal diameter or with the graft patency. Preoperative assessment of the regional left ventricular wall motion, on the other hand, was more valuable for prognosticating graft patency. Regions assessed as normal or hypokinetic had equally good graft patency, whereas akinetic or dyskinetic areas had only a 54% patency rate. Intraoperative measurement of the internal diameter of the vessel and graft flow were reliable predictors of graft patency: The larger the internal diameter and the greater the graft flow, the better the graft patency. Best surgical results can therefore be predicted when the internal diameter of the recipient vessel is 2.5 mm or more, graft flow is 100 ml/min or more, and the regional left ventricle moves well.

Time course of ischemic alterations during normothermic and hypothermic arrest and its reflection by on-line monitoring of tissue pH.

Currently there are no techniques available for the intraoperative on-line assessment of the adequacy of myocardial preservation during cardiac operation. The efficacy of a new intramyocardial pH electrode in quantitating myocardial ischemic damage and monitoring myocardial preservation was investigated by correlating changes in intramyocardial pH with the time course of metabolic, histologic, and ultrastructural alterations during global ischemia. Seventeen open-chest dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 2 hours. In Group I (n = 8), aortic cross-clamping was performed under normothermia. Group II (n = 9) received 4 degrees C potassium cardioplegia immediately after cross-clamping and consecutively every 30 minutes thereafter. Intramyocardial carbon dioxide tension (Pco2) and intramyocardial pH were measured continuously. Serial transmural biopsies were obtained before and at 5, 15, 30, 60, 90, and 120 minutes after cross-clamping for biochemical and structural analysis. During the period of cross-clamping, mean myocardial temperature was 33 degrees C in Group I and 19 degrees C in Group II. Intramyocardial pH at the end of 2 hours of anoxic arrest reached 5.39 +/- 0.08 in Group I and 6.49 +/- 0.13 in Group II (both values p less than 0.01 compared to prebypass values). Intramyocardial Pco2 rose from 41 +/- 4 to 234 +/- 13 mm Hg in Group I (p less than 0.001) and did not change in Group II. Tissue content of adenosine triphosphate (ATP) decreased by 51% in Group I and by 14% in Group II (p less than 0.01 compared to prebypass value). Tissue creatine phosphate was depleted in Group I and decreased by 48% in Group II. The degree of ischemic damage assessed by a mean ischemic score was 2.15 +/- 0.06 in Group I and 0.75 +/- 0.19 in Group II (p less than 0.001). Irreversible structural damage assessed by electron microscopy occurred in Group I 60 to 90 minutes after cross-clamping and was associated with an intramyocardial pH below 6.2. No such damage was observed in Group II. Therefore, intramyocardial pH is shown to be a reliable indicator of the severity of ischemic damage during anoxic arrest under normothermic conditions and of the adequacy of preservation under hypothermic conditions. Measurement of intramyocardial pH may provide a potentially useful tool for the intraoperative on-line monitoring of the adequacy of myocardial preservation in patients undergoing cardiac operation.

The superiority of continuous cold blood cardioplegia in the metabolic protection of the hypertrophied human heart.

The effects of sanguineous and asanguineous cardioplegia on the generation of myocardial acid in the hypertrophied human heart during aortic clamping and reflow were elucidated by continuous intraoperative monitoring of myocardial pH in 42 patients undergoing valve replacement, with or without coronary bypass. The patients were divided into three groups: Group I (n = 14) received intermittent crystalloid cardioplegia; group II (n = 14) received intermittent blood cardioplegia; and group III (n = 14) received continuous blood cardioplegia. The groups were matched according to six previously elucidated determinants of myocardial acidosis. Measurements were made of myocardial pH, hydrogen ion concentration ([H+]), and the difference in pH units between myocardial pH and the pH of neutrality of water at the corresponding temperature (delta pHn). Throughout aortic clamping, myocardial pH in groups I and II fell significantly by 0.46 +/- 0.08 and 0.15 +/- 0.07 units, respectively (p less than 0.001) between the groups). In contrast, myocardial pH remained statistically unchanged throughout aortic clamping in group III (p less than 0.001 compared to groups I and II). Similar relationships were observed in [H+] and delta pHn during aortic clamping. During the early reflow, myocardial acidosis was observed in all three groups and delta pHn in group III increased from -0.26 +/- 0.10 at the end of aortic clamping to -0.57 +/- 0.07 during reperfusion (p less than 0.03). Patients in groups II and III required significantly less inotropic and mechanical cardiac support than patients in group I (p = 0.017). Hence, although continuous blood cardioplegia does not completely prevent acid accumulation during reflow, it provides better metabolic protection of the hypertrophied human heart than either intermittent crystalloid or intermittent blood cardioplegia.

Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass.

Thirty-seven patients undergoing cardiopulmonary bypass operations were studied to assess the effect of skin temperature on platelet function. Differences in skin temperature between the two arms were created during bypass, at the completion of bypass, and at 2 and 24 hours after the completion of bypass. In each of 37 patients the temperature of one arm was increased with a water-filled blanket set at 40 degrees C. In 11 of these patients the other arm was allowed to equilibrate with the environment, and in the other 26 patients the arm was cooled with ice. Except for the differences in local skin temperature between the two arms, all factors known to affect the patient's bleeding time were similar. Measurements were made of bleeding times and the levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha in shed blood obtained at the template bleeding time site. In the 33 patients not treated with aspirin, local hypothermia produced an increased bleeding time and a significant reduction in the thromboxane B2 level at the bleeding time site, but no reduction in 6-keto-prostaglandin F1 alpha level. Local rewarming produced a significant increase in the shed blood thromboxane B2 level. In the four patients treated with aspirin, local hypothermia produced no differences in bleeding times or shed blood levels of thromboxane B2 or 6-keto-prostaglandin F1 alpha. These data show the benefits of rewarming patients with hypothermia who have nonsurgical blood loss to restore to normal both core and peripheral temperatures before resorting to the transfusion of homologous blood products.