Hours Of Cardioplegic Arrest Research Articles

Pulmonary injury after cardiopulmonary bypass: Beneficial effects of low-frequency mechanical ventilation

Pulmonary dysfunction is a frequent postoperative complication after cardiac surgery with cardiopulmonary bypass, and atelectasis is thought to be one of the main causes. The aim of this study was to evaluate whether low-frequency ventilation and continuous positive airway pressure during cardiopulmonary bypass reduce postcardiopulmonary bypass lung injury. Eighteen Yorkshire pigs were subjected to 120 minutes of cardiopulmonary bypass (1 hour of cardioplegic arrest) followed by 90 minutes of recovery before being sacrificed. Six animals served as control with the endotracheal tube open to atmosphere during cardiopulmonary bypass. The remaining animals were divided into 2 groups of 6: One group received continuous positive airway pressure of 5 cm H(2)O, and one group received low-frequency ventilation (5/minutes) during cardiopulmonary bypass. Lung tissue biopsy and bronchoalveolar lavage samples were obtained before and 90 minutes after discontinuation of cardiopulmonary bypass for measurement of adenine nucleotide (adenosine-5'-triphosphate, adenosine diphosphate, adenosine monophosphate), lactate dehydrogenase, DNA levels, and histology. Hemodynamic data and arterial blood gases were also collected through the study. The hemodynamic parameters were similar in the 3 groups. After cardiopulmonary bypass, the low-frequency ventilation group showed significantly better oxygen tension and alveolar arterial oxygen gradient, higher adenine nucleotide, lower lactate dehydrogenase levels, and reduced histologic damage in lung biopsy, as well as lower DNA levels in bronchoalveolar lavage compared with the control group. The continuous positive airway pressure group showed only significantly reduced lactate dehydrogenase levels compared with control. Low-frequency ventilation during cardiopulmonary bypass in a pig experimental model reduces tissue metabolic and histologic damage in the lungs and is associated with improved postoperative gas exchange.

Early gene expression profiles during intraoperative myocardial ischemia-reperfusion in cardiac surgery

The effects of cold cardioplegic arrest and reperfusion on human ventricular gene expression are unknown. We tested the hypothesis that intraoperative ischemia-reperfusion under conditions of blood cardioplegic arrest would induce a unique myocardial genomic profile indicative of a cardioprotective response. Right ventricular samples were serially acquired during surgical repair of ventricular septal defect. Expression profiling revealed 3 patterns of gene expression: (1) increased expression above control levels within 1 hour of cardioplegic arrest, with further amplification during early reperfusion; (2) increased expression limited to the reperfusion phase; and (3) reduced expression during reperfusion. Functional annotation and network mapping of differentially expressed genes indicated activation of multiple signaling pathways regulated by phosphatidylinositide 3'-OH kinase convergent on cellular growth and reparative programs. Also observed was increased expression of genes regulating hemoglobin synthesis, suggesting a novel cardioprotective pathway evoked during ischemia-reperfusion. Reversible myocardial ischemia-reperfusion during cardiac surgery is associated with an immediate genomic response that predicts a net cardioprotective phenotype.

Multiple Treatment Approach to Limit Cardiac Ischemia-Reperfusion Injury

This study evaluates a multiple treatment approach (ie, pharmacologic preconditioning [diazoxide], sodium-proton exchange inhibition [cariporide], and controlled reperfusion) to improve the outcome from severe cardiac ischemia-reperfusion injury that occurs during a cardiac operation. Five groups of 10 pigs (group 1: control, group 2: diazoxide, group 3: cariporide, group 4: controlled reperfusion, and group 5: combination of diazoxide and cariporide-controlled reperfusion) underwent 75 minutes of left anterior descending occlusion, 1 hour of cardioplegic arrest, and 2 hours of reperfusion. Prior to occlusion, each group received an infusion of vehicle alone (ie, dimethylsulfoxide for the control and the controlled reperfusion groups) or vehicle with drug (ie, diazoxide or cariporide, or both for all other groups). Infarct size (primary outcome) was measured and was normalized to the region at risk. Regional function (secondary outcome) was measured using preload recruitable work area. Infarct size as a function of area at risk was decreased by cariporide-controlled reperfusion, and combination treatment compared with the control group (14 +/- 6%, 15 +/- 8%, and 9 +/- 4% vs 24 +/- 9%; p < 0.02), and variation in infarct size was decreased by combination treatment compared with the controlled reperfusion group alone (p < 0.02). Recovery of systolic function during reperfusion significantly improved in the left anterior descending region in the cariporide and combination groups compared with the control, controlled reperfusion, or diazoxide groups (group-time effect, p < 0.05). Combined use of controlled reperfusion, cariporide, and diazoxide decreases myocyte necrosis and loss of systolic function compared with an untreated control group. Combination treatment has the potential to improve the results of cardiac surgery, however further improvements are needed before clinical application.

Initial reperfusion with magnesium after cardioplegic arrest attenuates myocardial reperfusion injury.

Magnesium's effect on calcium ion concentrations may attenuate myocardial reperfusion injury. The aim of this study was therefore to investigate the effects on the recovery of myocardial function of initial reperfusion with varying Mg(2+) concentrations following cardioplegic arrest. Isolated guinea pig hearts underwent 3.5 hours of cardioplegic arrest in St. Thomas Hospital II solution (STH) or Bretschneider HTK solution (HTK) at 24 degrees C. Control hearts were reperfused with normal Krebs-Henseleit solution (KHS). In the therapy groups, hearts were initially reperfused with 5, 10, or 20 mM Mg(2+) for 15 minutes, followed by 30 minutes of perfusion with KHS. During initial reperfusion, elevated Mg(2+) concentrations markedly reduced rate-pressure product, dP/dt and O 2 demand. Release of LDH and CK was reduced in the therapy groups pretreated with Bretschneider HTK. After Mg(2+) washout, left ventricular function recovery and compliance was improved after HTK but not after STH cardioplegia. Following both STH and HTK cardioplegia, Mg(2+) reperfusion reduced reperfusion arrhythmias. The combination of HTK cardioplegia with 15 min initial Mg(2+) (5 and 10 mM, but not 20 mM) reperfusion was clearly superior to HTK followed by immediate Krebs-Henseleit reperfusion as well as STH cardioplegia with or without initial Mg(2+) reperfusion. The high Mg(2+) concentrations in the STH solution might mask beneficial effects of Mg(2+) reperfusion.

Ischemic preconditioning and Na +/H + exchange inhibition improve reperfusion ion homeostasis

Background. Intramyocyte sodium (Na +) increases during ischemia and reperfusion, which causes myocardial calcium (Ca 2+) uptake and leads to myocyte injury or death. This study determines if ischemic preconditioning and myocyte sodium-hydrogen ion (Na +-H +) exchange (NHE) inhibition decreases Na + gain that otherwise occurs with cardioplegic arrest and reperfusion. Methods. Pigs had 1 hour of cardioplegic arrest followed by reperfusion. Group 1 had no intervention (controls). Group 2 received dimethyl amiloride (DMA, an NHE inhibitor), and group 3 had ischemic preconditioning before cardioplegic arrest. Precardioplegia to postreperfusion change in intramyocyte ion content was measured with atomic absorption spectrometry. The time to initial electrical activity and number of defibrillations needed to establish an organized rhythm postreperfusion were used as electrophysiologic variables to measure ischemia-reperfusion injury. Results. Intramyocyte Na + content for group 1 increased from 45.9 ± 6.7 to 61.9 ± 22.5 μmol/g ( p = 0.02). Group 2 had an insignificant decrease in intramyocyte Na + of 27.7 ± 19.58 μmol/g ( p = 0.06), and group 3 had an insignificant decrease of 10.8 ± 46.33 μmol/g ( p = 0.48). Interstitial water increased significantly in all groups, but there were no significant increases in intramyocyte water content. Electrophysiologic recovery was similar for all three groups. Conclusions. The NHE inhibition and ischemic preconditioning each eliminated the increase in intramyocyte Na + content that otherwise occurred with cardioplegic arrest and reperfusion in this porcine model. Because their mechanisms are distinct, it is possible that an additive beneficial effect against ischemia-reperfusion injury can be achieved by using NHE inhibition together with a preconditioning stimulus as prereperfusion therapy.

Role of endogenous endothelin on coronary reflow after cardioplegic arrest

Objective: Endothelin plays a role in the regulation of basal coronary tone. We hypothesized that low coronary reflow and reduced cardiac function after prolonged ischemia may be due to increased release of endogenous endothelin. Methods: Using an isolated perfused rat heart, we examined the effect of the addition of various endothelin antagonists during reperfusion after 4 hours of cardioplegic arrest at 4°C. Hearts were freeze-clamped at the end of reperfusion for analysis of high-energy phosphate levels. Results are expressed as the percentages of preischemic values. Results: The addition of bosentan or Ro61-0612 (nonselective endothelin antagonists) resulted in a significant increase in the recovery of coronary flow after 30 minutes of reperfusion (100.9% vs 85.3% [P =.03] and 122.4% vs 83.7% [P <.001], respectively, versus controls). The addition of PD155080 (endothelin A antagonist) had a similar effect (129.5% vs 91.4%, P =.008). BQ788 (endothelin B antagonist) and phosphoramidon (endothelin-converting enzyme inhibitor) had no effect. Myocardial adenosine triphosphate levels were significantly (12.1%) higher after reperfusion with Ro61-0612 (18.1 ± 0.4 μmol/g vs 16.2 ± 0.5 μmol/g, P =.01). There was no difference in the recovery of cardiac mechanical function with any of the antagonists studied. Conclusion: These results suggest that endogenous endothelin plays a role in low coronary reflow after prolonged cardioplegic arrest but does not impair recovery of myocardial function.

Ventricular dysfunction after cardioplegic arrest is improved after myocardial gene transfer of a beta-adrenergic receptor kinase inhibitor.

Acute cardiac contractile dysfunction is common after cardiopulmonary bypass (CPB). A potential molecular mechanism is enhanced beta-adrenergic receptor kinase (betaARK1) activity, because beta-adrenergic receptor (betaAR) signaling is altered in cardiomyocytes after cardioplegia. Therefore, we examined whether adenovirus-mediated intracoronary delivery of a betaARK1 inhibitor (Adv-betaARKct) could prevent post-CPB dysfunction. Rabbits were randomized to receive 5x10(11) total viral particles of Adv-betaARKct or PBS. After 5 days, hearts were arrested with University of Wisconsin solution, excised, and stored at 4 degrees C for 15 minutes or 4 hours before reperfusion on a Langendorff apparatus. Left ventricular (LV) function measured by end-diastolic pressure response to preload augmentation, contractility (LV dP/dt(max)), and relaxation (LV dP/dt(min)) was assessed by use of increasing doses of isoproterenol and compared with a control group of nonarrested hearts acutely perfused on the Langendorff apparatus. In the PBS-treated hearts, LV function decreased in a temporal manner and was significantly impaired compared with control hearts after 4 hours of cardioplegic arrest. LV function in Adv-betaARKct-treated hearts, however, was significantly enhanced compared with PBS treatment and was similar to control nonarrested hearts even after 4 hours of cardioplegia. Biochemically, several aspects of betaAR signaling were dysfunctional in PBS-treated hearts, whereas they were normalized in betaARKct-overexpressing hearts. Myocardial gene transfer of Adv-betaARKct stabilizes betaAR signaling and prevents LV dysfunction induced by prolonged cardioplegic arrest. Thus, betaARK1 inhibition may represent a novel target in limiting depressed ventricular function after CPB.

Cold cardioplegic arrest enhances heat shock protein 70 in the heat-shocked rat heart

Background: Myocardial content of the 70-kd heat shock protein has been found to correlate with improved cardiac recovery after ischemia, but the mechanisms and conditions that regulate its level, particularly under clinical conditions, are unclear. The aim of this study was to assess the effect of hypothermic cardioplegic arrest and reperfusion on the expression of 70-kd heat shock protein in a protocol mimicking conditions of preservation for cardiac transplantation. Methods: Heat-shocked and control hearts were subjected to 4 hours of cardioplegic arrest and global ischemia at 4°C and then to 20 minutes of reperfusion. Hearts were freeze clamped at different time points—after 15 minutes of Langendorff perfusion, at the end of ischemia, and after 20 minutes of reperfusion, and analyzed for heat shock protein 70 content by Western blotting. Another set of hearts was subjected to 10 minutes of normothermic ischemia and 20 minutes of reperfusion followed by freeze clamping and analysis of heat shock protein 70 content as in cardioplegic arrest protocol. Cardiac function was measured by means of a left ventricular balloon at the end of reperfusion. Results: Preischemic concentration of 70-kd heat shock protein was increased in heat-shocked hearts compared with control hearts. The content of 70-kd heat shock protein in heat-shocked hearts was further increased from 5.0 ± 2.4 ng/μg at the end of ischemia to 11.0 ± 4.9 ng/μg (n = 8, mean ± SD; P <.05) at 20 minutes of reperfusion after cold cardioplegic arrest. No further rise in 70-kd heat shock protein of the heat-shocked hearts was observed after normothermic ischemia. Maximal developed pressure was 120.8 ± 13.4 mm Hg in control hearts compared with 164.7 ± 22.5 mm Hg in heat-shocked hearts (n = 5, mean ± SD; P =.037) after cardioplegic arrest. By contrast, after normothermic ischemia, maximum developed pressure was 111.2 ± 10.9 mm Hg in control hearts compared with 139.2 ± 11.0 mm Hg in heat-shocked hearts (n = 4, mean ± SD; P =.031). Conclusion: Hypothermic cardioplegic arrest but not short normothermic ischemia triggered a further increase in the level of 70-kd heat shock protein in heat-shocked rat hearts, which may enhance endogenous cardiac protection. (J Thorac Cardiovasc Surg 2001;121:1130-6)

Age dependence of heat stress mediated cardioprotection

Background. To study the influence of age on heat stress cardioprotection, functional recovery, nucleotide concentrations, and heat stress protein 70 (Hsp70) levels were compared in the heat stressed (HS) and control (C) hearts at different ages, in a protocol mimicking donor heart preservation for transplantation. Methods. Control and heat stressed (24 hours before experiment) rat hearts were divided into three age groups: (I) 1 month, (Y) 4 months, and (M) 16 months (n = 6). Left ventricle balloon catheter was used to determine systolic and end-diastolic pressure/volume relations before and after 4 hours of cardioplegic arrest at 4°C. Another identical set of isolated hearts underwent 5 minutes of normoxic perfusion to obtain preischemic Hsp70 content and metabolite concentrations. Results. The postischemic recovery was highest in group HS-Y as compared to C-Y, HS-I, C-I, HS-M, and C-M. There were no differences in preischemic adenine nucleotides or creatine metabolite concentrations between the three age groups. In contrast, the nicotinamide adenine dinucleotide (oxidized form) (NAD +) and nicotinamide adenine dinucleotide phosphate (oxidized form) (NADP +) concentrations were significantly raised in group HS-Y. Hsp70 content was increased in all HS groups with no difference between the age groups. Conclusions. Improved postischemic functional recovery after cardioplegic arrest was observed in the young adult HS hearts. This was associated with highest NAD + and NADP + concentrations and did not correlate with increased Hsp70 content.

Controlled postcardioplegia reperfusionMechanism for attenuation of reperfusion injury

Objective: Controlled reperfusion and secondary cardioplegia are used to minimize reperfusion injury. The mechanisms for their benefit are incompletely defined and may include attenuation of myocyte sodium uptake. Methods: Pigs had 1 hour of cardioplegic arrest followed by reperfusion with blood (control) or warm cardioplegic solution followed by blood (test). Reperfusion injury in the control and test groups was quantified by measuring changes of intramyocyte ion content with atomic absorption spectrometry and by analyzing electrophysiologic recovery from recordings of reperfusion arrhythmias. Results: Control animals had an increase in intramyocyte sodium content at 5 minutes after initiating reperfusion (+20.2 μmol/g dry weight, P < .04), whereas the test group had an insignificant decrease (–14.0 μmol/g dry weight, P = .33). The first rhythm after initiating reperfusion was more often ventricular fibrillation in the control group (100% vs 50%, P < .02), and the control group required more defibrillations to establish a nonfibrillating rhythm (4.5 ± 1.2 vs 1.1 ± 0.3, P < .03). Conclusions: Controlled reperfusion eliminated the increase in intramyocyte sodium that was observed in the control group at 5 minutes after cardioplegic arrest. This improvement in myocyte ion homeostasis during postcardioplegia reperfusion was associated with fewer reperfusion arrhythmias. These data support the hypothesis that attenuation of myocyte sodium gain during postischemic reperfusion is a mechanism by which controlled reperfusion and secondary cardioplegia are beneficial. (J Thorac Cardiovasc Surg 2000;119:1093-101)

Continuous Perfusion Improves Preservation of Donor Rat Hearts: Importance of the Implantation Phase

Background. Continuous hypothermic perfusion of donor hearts may provide extra protection for long ischemic times and suboptimal donors. The aim of three separate studies was to assess the effect of continuous hypothermic perfusion during simulated donor heart storage and implantation. Methods. In study 1 twelve isolated rat hearts underwent 10 minutes of normothermic ischemia to simulate the effect of brain death on the heart and 5 hours of cardioplegic arrest, using University of Wisconsin solution. Six hearts were statically stored in University of Wisconsin solution at 2°C, and six were perfused with University of Wisconsin solution. To assess the effect of simulated implantation, in study 2 an additional 12 hearts were statically stored for 5.5 hours in University of Wisconsin solution, six of which were rewarmed to a mean of 16°C over the last 30 minutes of arrest. To assess the effect of simulated perfusion, in study 3 during implantation 12 hearts were rewarmed to a mean of 16°C over the last 30 minutes of arrest, during which time six were perfused with 2°C solution. Results. Hearts perfused during storage demonstrated greater recovery of prearrest power, 85.8% ± 1.8%, than hearts preserved by static storage, 72.7% ± 3.0% ( p < 0.01). The simulated warm implantation period reduced recovery of power from 68.3% ± 5.1% to 40.2% ± 2.0% ( p < 0.001). Perfusion during warm implantation improved recovery to 61.8% ± 3.9% ( p < 0.01). In all experiments improved function was accompanied by improved metabolic energy status. Conclusions. During the implantation period of heart transplantation the donor heart sustains injury that could amount to 50% of total ischemic injury. Continuous perfusion during the cold storage phase and during simulated implantation improves recovery of the donor heart.

Protein kinase C activation before cardioplegic arrest: Beneficial effects on myocyte contractility

Objective: A potential intracellular mechanism for the protective effects of myocardial preconditioning is the activation of protein kinase C. The present study tested the hypothesis that a brief period of protein kinase C activation before cardioplegic arrest would provide protective effects on myocyte contractility with subsequent reperfusion and rewarming. Methods: Left ventricular porcine myocytes were assigned to the following treatments: (1) Protein kinase C/cardioplegia: Protein kinase C activation in myocytes ( n = 39) for 3 minutes with a phorbol ester (10 −9 mol/L of phorbol 12-myristate 13-acetate) in oxygenated, normothermic (37° C) cell media. Protein kinase C activation was followed by 2 hours of cardioplegic arrest (K +, 24 mEq/L; HCO 3 –, 30 mEq/L; 4° C) and a 5-minute reperfusion period (37° C media). (2) Cardioplegia: Myocytes ( n = 31), 2 hours of cardioplegic arrest, and a 5-minute reperfusion and rewarming period. Myocyte contractility was measured by means of high-speed videomicroscopy. For comparison purposes, contractile function was examined in myocytes ( n = 70) under normothermic control conditions. Results: Myocyte shortening velocity was reduced after cardioplegic arrest when compared with normothermic values (22.3 ± 1.6 vs 48.8 ± 2.0 μm/sec, p < 0.0001). Protein kinase C activation before cardioplegic arrest normalized myocyte shortening velocity (48.8 ± 2.5 μm/sec). Co-incubation with phorbol 12-myristate 13-acetate and chelerythrine (10 −6 mol/L), an inhibitor of protein kinase C, before cardioplegic arrest abolished the protective effects of phorbol 12-myristate 13-acetate pretreatment. Conclusion: These results suggest that an endogenous means of providing improved myocardial protection during prolonged cardioplegic arrest can be achieved through a brief period of protein kinase C activation. (J Thorac Cardiovasc Surg 1997;114:651-9)

Anti-CD11b monoclonal antibody improves myocardial function after six hours of hypothermic storage

The shortage of pediatric heart donors often necessitates considerable travel time and, as a result, prolonged donor heart ischemia. This excessive hypothermic storage may contribute markedly to myocardial dysfunction in the recipient. We investigated the role of leukocyte-endothelial interactions in this dysfunction in an isolated, immature (mean age, 11.8 +/- 1.6 days) swine heart model using a monoclonal antibody against a leukocyte adhesion molecule. We studied a total of 20 hearts subjected to 6 hours of cardioplegic arrest at 4 degrees C. Group M1/70 (n = 6) received at reperfusion 15 micrograms/mL of a monoclonal antibody F(ab')2 fragment to CD11b, the alpha-subunit of the leukocyte adhesion molecule Mac-1. Group MB10.6 (n = 8) received 15 micrograms/mL of the swine unreactive F(ab')2 MB10.6, and the third group received saline vehicle. Administration of M1/70 resulted in improved postischemic recovery of ventricular function compared with the two control groups (p < 0.05). These data implicate leukocyte-endothelial interactions mediated by the leukocyte adhesion molecule CD11b in myocardial dysfunction after long-term hypothermic ischemia. Specific antiadhesion strategies such as this may safely extend storage time for pediatric donor hearts.

Adverse effects of low-pressure reperfusion after hypothermic cardioplegia in normal and hypertrophic hearts

The aim of this study was to determine the effect of low-pressure and high-pressure reperfusion, with and without ventricular fibrillation, on the recovery of hypertrophic and normal hearts after hypothermic cardioplegia. Fourteen hearts rendered hypertrophic by valvular aortic stenosis and 18 normal canine hearts were subjected to 1 hour of cardioplegic arrest at 28 degrees C during cardiopulmonary bypass. Each heart was then reperfused at a coronary pressure of either 40 mm Hg (low) or 80 mm Hg (high), initially in the empty beating state and then during ventricular fibrillation. Low-pressure reperfusion produced left ventricular subendocardial ischemia in hypertrophic and in normal hearts, shown by marked depression of subendocardial blood flow, myocardial pH, and myocardial oxygen consumption. In hypertrophic hearts the ischemia was more severe and resulted in a persistent depression of left ventricular function and myocardial oxygen consumption even when coronary pressure was returned to normal levels. High-pressure reperfusion was associated with rapid and complete recovery of myocardial metabolism and function in hypertrophic and in normal hearts. During low-pressure reperfusion, ventricular fibrillation exacerbated ischemia in hypertrophic and in normal hearts. During high-pressure reperfusion, a short period of ventricular fibrillation produced no adverse effects either in hypertrophic or in normal hearts. We conclude that low-pressure reperfusion produces subendocardial ischemia in normal and in hypertrophic hearts even in the empty beating state; in hypertrophic hearts it also impairs recovery of myocardial metabolism and function. The adverse effects of low-pressure reperfusion are exacerbated by ventricular fibrillation.

Myocardial protection in the hypertrophied right ventricle

Hypertrophied right ventricle presents a sensitive state that may not be adequately protected by modern cardioplegic methods. Cardiac metabolism, performance, and ultrastructure were measured in response to 1 hour of cardioplegic arrest in 15 pigs with right ventricular hypertrophy using intermittent hypothermic crystalloid, blood, and Fluosol DA 20%-based cardioplegia. Reperfusion time was 1 hour. One hour after a 60-minute cross-clamp period, there were no differences in light microscopy. Total energy stores increased in 4 of 5 animals given blood cardioplegia compared with 1 of 5 for each of the other groups. Cardiac performance data also showed better results for animals treated with blood cardioplegia. After 30 minutes of reperfusion, animals receiving blood cardioplegia recovered 131% ± 42% of preoperative systolic performance compared with 106% ± 49% for Fluosol-treated animals and only 82% ± 27% recovery for the crystalloid-treated group. After 60 minutes of reperfusion, the blood group showed 119% ± 20% recovery compared with 89% ± 23% and 85% ± 50% recovery for Fluosol- and crystalloid-treated hearts, respectively. In conclusion, blood cardioplegia provided better protection than did crystalloid or Fluosol DA 20% cardioplegia when animals with right ventricular hypertrophy underwent 1 hour of cardioplegic arrest. It may have repaired damaged myocardium, leaving better hearts after cross-clamping than before.

The efficacy of blood cardioplegia is not due to oxygen delivery

Twenty-seven canine hearts instrumented with ultrasonic dimension crystals underwent simultaneous determination of stroke work and myocardial oxygen consumption during incremental volume loading on right heart bypass before and 30 minutes after 2 hours of cardioplegic arrest at 10 degrees C. Three cardioplegic solutions were used: Hematocrit values were 17.0% (group I), 8.2% (group II), and 0% (group III). In all groups the slope of the linear stroke work versus end-diastolic volume relationship, a measure of contractility, was unchanged after ischemic arrest. However, the myocardial oxygen consumption for basal metabolism was increased an average of 25.5% after arrest with plasma (group III). Since the plasma concentration in all three groups was identical, and the oxygen available to the hearts during ischemia was the same in groups II and III, the efficacy of blood-based cardioplegic solutions cannot be attributed to a plasma component or to the greater oxygen-carrying capacity of the red blood cell. Future studies should attempt to identify the salutory entity of the red cell responsible for preservation of myocardial oxygen consumption efficiency.

Enhanced myocardial preservation by nicotinic acid, an antilipolytic compound: Improved cardiac performance after hypothermic cardioplegic arrest

The effect of nicotinic acid, an antilipolytic drug, on myocardial preservation was studied on the basis of cardiac performance after 2 hours of cardioplegic arrest. Isolated in situ pig hearts were subjected to 120 minutes of hypothermic potassium (35 mEq) crystalloid cardioplegic arrest followed by 60 minutes of reperfusion. The experimental group received nicotinic acid 0.08 mmol/L 15 minutes before cardioplegic arrest, whereas the control group received 15 minutes of unmodified perfusion. There was a marked decline in myocardial creatine phosphate levels during cardioplegic arrest in both groups that returned to the baseline level during reperfusion without a significant intergroup difference, and adenosine triphosphate levels remained stable throughout the experiment in both groups. Myocardial oxygen consumption during reperfusion was significantly higher in hearts treated with nicotinic acid, which was consistent with a significantly greater cardiac contractile force as evaluated by isovolumetric left ventricular pressure measurements. There appeared to be less cardiac membrane damage as measured by creatine kinase release during reperfusion, which was significantly inhibited by treatment with nicotinic acid. The present study supports the conclusion that nicotinic acid improves cardiac performance after hypothermic cardioplegic arrest.

Improved Myocardial Protection by Creatine Phosphate in Cardioplegic Solution. An In Vivo Study in the Pig During Normothermic Ischemia

The effect of creatine phosphate in potassium cardioplegia was studied in a pig heart model in vivo. Fifteen pigs divided into two groups were placed on cardiopulmonary bypass and subjected to 1 hour of cardioplegic arrest at normothermia. In group I (control), in which a potassium cardioplegic solution was used, only two out of eight animals could successfully be weaned from bypass. In group II, on the other hand, in which creatine phosphate (10 mmol/l) was added to the cardioplegic solution, six out of seven animals could be weaned from bypass and the heart performance assessed by volume loading. Group II also exhibited better maintenance of high-energy phosphates during ischemia, with significantly higher adenylate charge potential, than group I. In all animals weaned from bypass--two in group I and six in group II--the ventricular performance was decreased compared with that before induction of ischemia. The results indicate that creatine phosphate could be an effective constituent in potassium cardioplegia.

Prevention of Ischemia-Induced Myocardial Platelet Deposition by Exogenous Prostacyclin

The antithrombotic effects of prostacyclin infusion on myocardial platelet deposition were studied in a canine model during and after global ischemia. Eleven isolated heart preparations were subjected to 1 hour of cardioplegic arrest under moderate hypothermia (27° to 28° C), including a control group (n = 7) and a prostacyclin-treated group (n = 4). The hearts of four other dogs were continuously perfused for 180 minutes. Platelet deposition was measured at 15 minute intervals throughout the 3 hour study. Serial full-thickness myocardial biopsy specimens were analyzed for activity of 111In-labeled platelets with 99mTc-labeled erythrocyte correction for tissue blood content The pattern of platelet distribution was determined by scintiscans of each heart, taken with a gamma camera at the end of the 60 minute reperfusion period. Substantial myocardial platelet deposition was found in the control hearts after ischemia but not in the prostacyclin-treated group (p

Myocardial energetics after thermally graded hyperkalemic crystalloid cardioplegic arrest

Previous studies assessing the efficacy of myoprotective regimens have compared preischemic and postischemic myocardial oxygen consumption within a limited range of cardiac performance. However, recent data suggest that ischemia-induced perturbations in myocardial energetics may occur only when the left ventricle develops physiologic pressures. Therefore, in canine hearts supported by cardiopulmonary bypass, myocardial oxygen consumption (ml oxygen X 10(-2)/beat/100 gm left ventricular weight) was determined during incremental isovolumic pressure-volume loading before and 30 minutes after 2 hours of cardioplegic arrest. The ischemic insult was graded by maintaining myocardial temperature at 12 degrees C (Group I, n = 6), 20 degrees C (Group II, n = 7), or 28 degrees C (Group III, n = 6). Postischemic Starling curves were unchanged in Groups I and II but depressed 53% in Group III hearts (p less than 0.005). In Group I, postischemic myocardial oxygen consumption at specific peak developed pressures was similar to preischemic oxygen consumption. In contrast, postischemic Group II and III hearts consumed 39% more oxygen than preischemically when peak developed pressure exceeded 75 mm Hg (p less than 0.01). Postischemic hearts demonstrated reciprocal changes in arteriovenous oxygen content difference (24%, 30%, and 34% lower than preischemic values for Groups I, II, and III, respectively) and coronary blood flow (156%, 195%, and 192% higher than preischemic values for Groups I, II, and III, respectively). Only in Group II and III hearts did the increased coronary blood flow offset the defect in oxygen extraction such that myocardial oxygen consumption was increased. These data suggest that inefficient utilization of oxygen when the heart is developing physiologic pressures is a sensitive marker for myocardial injury after crystalloid cardioplegic arrest.