Russell F. Stahl

Reduction of bleeding after heart operations through the prophylactic use of epsilon-aminocaproic acid

UNLABELLED Excessive postoperative bleeding after heart operations continues to be a source of morbidity. This prospective double-blind study evaluated epsilon-aminocaproic acid as an agent to reduce postoperative bleeding and investigated its mode of action. One hundred three patients were randomly assigned to receive either 30 gm epsilon-aminocaproic acid (51 patients) or an equivalent volume of placebo (52 patients). In a subset of these patients (14 epsilon-aminocaproic acid, 12 placebo), tests of platelet function and fibrinolysis were performed. RESULTS By multivariate analysis, three factors were associated with decreased blood loss in the first 24 hours after operation: epsilon-aminocaproic acid versus placebo (647 ml versus 839 ml, p = 0.004), surgeon 1 versus all other surgeons (582 ml versus 978 ml, p = 0.002), and no intraaortic balloon versus intraaortic balloon pump use (664 ml versus 1410 ml, p = 0.02). No significant differences in platelet function could be demonstrated between the two groups. Inhibited fibrinolysis, as reflected by less depression of the euglobulin clot lysis and no rise in D-dimer levels, was significant in the epsilon-aminocaproic acid group compared with the placebo group. CONCLUSION The intraoperative use of epsilon-aminocaproic acid reduces postoperative cardiac surgical bleeding.

Decreasing myocardial pH reflects ischemia during continuous warm retrograde cardioplegic arrest

Warm continuous retrograde cardioplegia is thought to prevent myocardial ischemia. We tested this hypothesis by subjecting canine hearts to 2 hours of either antegrade or retrograde perfusion with normothermic blood cardioplegia. Ischemic alterations were evaluated through the measurement of myocardial pH, tissue levels of adenosine triphosphate and lactate, and the preservation of left ventricular contractility. Antegrade perfusion resulted in uniformly positive changes in the myocardial pH in both ventricles, preserved levels of adenosine triphosphate, and small increases in the myocardial lactate levels. In contrast, retrograde perfusion caused the myocardial pH to decrease, especially in the right ventricle. Tissue lactate levels rose to a significantly greater extent during retrograde perfusion and adenosine triphosphate levels declined, although not to a statistically significant degree. Finally, myocardial function, as assessed by the preload recruitable work area, was preserved (103% +/- 20% of baseline) in the antegrade group but was markedly diminished (33% +/- 6%) in retrogradely perfused left ventricles 35 minutes after the aortic cross-clamp was removed. These data suggest that ischemic metabolism and the subsequent alteration of myocardial function take place despite continuous retrograde perfusion with normothermic blood cardioplegia.

Retrograde coronary sinus perfusion provides non-homogeneous myocardial blood flow

The ability of retrograde cardioplegia to protect the right ventricle has been questioned. Canine myocardial circulation was assessed by infusing colored microspheres through the coronary sinus. The relative flow index (RFI), a normalized measure of tissue blood flow, was determined for 76 sections of myocardium. Three distinct flow regions were evident from these measurements. A paucity of blood flow through some basal sections of the right ventricle (RFI = 0.23 +/- 0.19) was found to be significantly different (p < 0.005) from regions of the heart with normal flow (RFI = 1.12 +/- 0.06). Sections from the right ventricular apex demonstrated augmented flow (RFI = 3.72 +/- 1.18). These data indicate that retrograde coronary perfusion provides nonuniform flow and under some conditions may provide inadequate perfusion to portions of the right ventricle.

Retrograde abdominal visceral perfusion: Is it beneficial?

BACKGROUND It is proposed that retrograde abdominal perfusion be used in combination with retrograde cerebral perfusion to provide total body visceral protection during aortic reconstruction; however, its physiologic effects remain unknown. METHODS We compared the effect of superior vena caval perfusion alone with that of combined superior and inferior vena caval perfusion on the liver and kidney in 6 mongrel dogs. Organ blood flow was measured using ultrasonic flow probes on the hepatic artery, the portal vein, and the renal artery. Regional tissue blood flow to the liver and the kidney was assessed using colored microspheres and pH probes. Anesthetized dogs were placed on total cardiopulmonary bypass. After cooling to 20 degrees C, retrograde perfusion was begun with 30 minutes of superior vena caval perfusion followed by another 30 minutes of bicaval perfusion, or vice versa. RESULTS Very little renal blood flow was measured with either method of retrograde perfusion. Although the liver received more blood flow in comparison to the kidney, there was no significant difference between superior vena caval perfusion alone and bicaval perfusion. The addition of inferior vena caval perfusion results in portal hypertension, hepatic congestion, ascites, and bowel edema. CONCLUSIONS In the canine model, bicaval perfusion does not provide superior protection to the liver and kidneys when compared with superior vena caval perfusion alone.

Diminished Myocardial Function Precedes Tissue Acidosis during Coronary Hypoperf usion

The current study sought to elucidate the relationship between myocardial pH and function during a significant but not absolute reduction in coronary flow. In a canine model, a partial coronary arterial stenosis was created, with the left anterior descending coronary artery (LAD) flow reduced by 50% compared to prestenosis levels, and maintained at that level for the duration of the study. During the experiment, interstitial myocardial pH and regional myocardial function, as assessed by the regional preload recruitable work area (PRWA), were measured. PRWA was depressed to 60% of baseline values, on average, for the entire period of reduced LAD flow. In contrast to the pattern observed with myocardial blood flow and systolic function, metabolic evidence of myocardial ischemia, that is, reduced myocardial pH did not become significantly different from baseline levels until after LAD flow had been reduced for 15 min. Thus, measurable changes in myocardial pH appeared slowly over time despite the fact that regional myocardial blood flow was decreased immediately. Therefore, myocardial pH cannot be used to anticipate alterations in myocardial contractile function.

Hypothermic cardioplegic arrest is associated with increased myocardial adenosine.

The current study examined the effects of temperature on myocardial pH, contractile function and adenosine triphosphate metabolism, particularly the production of adenosine. We matched intermittent delivery of blood cardioplegia in two groups (hypothermia 15 degrees C; normothermia 37 degrees C), for 2 h of cardioplegic arrest. Hypothermic perfusion resulted in a markedly alkalotic pH, and nearly a threefold increase in adenosine and adenosine monophosphate levels compared to normothermic hearts. Tissue levels of adenosine triphosphate were preserved to the same extent in each group, despite the increased energy requirements of normothermia. Myocardial contractile function was not statistically different between the two groups at 30 min and 2 h after the cross clamp was removed. These data suggest that both methods, hypothermia via its reduced energy demands, and normothermia through continued glycolytic metabolic activity, allow the myocardium to maintain energy stores and resume adequate function. However, hypothermic perfusion results in an accumulation of adenosine, demonstrating that temperature should be considered when attempting to manipulate the generation and accumulation of the compound.

Sensor materials for an intravascular fiber optic nitric oxide sensor

Nitric oxide (NO) is an important regulatory molecule in physiological processes including neurotransmission and the control of blood pressure. It is produced in excess during septic shock, the profound hypotensive state which accompanies severe infections. In-vivo measurement of NO would enhance the understanding of its varied biological roles. Our goal is the development of an intravascular fiber-optic sensor for the continuous measurement of NO. This study evaluated nitric oxide sensitive compounds as potential sensing materials in the presence and absence of oxygen. Using absorption spectroscopy we studied both the Fe II and Fe III forms of three biologically active hemes known to rapidly react with NO: hemoglobin, myoglobin, and cytochrome-c. The Fe II forms of hemoglobin and myoglobin and the Fe III form of cytochrome-c were found to have the highest sensitivity to NO. Cytochrome c (Fe III) is selective for NO even at high oxygen levels, while myoglobin is selective only under normal oxygen levels. NO concentrations as low as 1 (mu) M can be detected with our fiber-optic spectrometer using cytochrome c, and as low as 300 nM using myoglobin. Either of these materials would be adequate to monitor the increase in nitric oxide production during the onset of septic shock.