Coronary Perfusate Research Articles

Effect of perfusate rheology on the diastolic coronary pressure-flow relationship

The hypothesis that rheological properties of the coronary perfusate account for the curvilinearity and high zero-flow pressure (Pf = 0) of the diastolic coronary-pressure flow relationship (DCPFR) was tested by measuring these relationships using coronary perfusates of varying rheological character. In 16 open-chest, heart-blocked dogs the left circumflex coronary artery was cannulated and perfused using an extra-corporeal circuit, and autoregulation was abolished with intracoronary adenosine. DCPFRs were constructed from data obtained at multiple steady-state levels of coronary pressure during long diastoles while left ventricular diastolic pressure was held constant. Although isovolumic hemodilution reduced hematocrit from 46 +/- 3% to 32 +/- 3% and increased coronary conductance, it neither abolished the curvilinearity nor changed Pf = 0, which remained significantly higher than left ventricular diastolic pressure. In 10 additional animals, DCPFRs obtained during blood perfusion were compared with those obtained using crystalloid perfusate. Crystalloid perfusion increased coronary conductance and failed to abolish curvilinearity. However, with crystalloid perfusate, Pf = 0 was reduced to a value essentially equal to left ventricular diastolic pressure. We conclude that while the rheological properties of coronary perfusates do not fully account for the curvilinearity of the DCPFR, they do importantly influence coronary conductance and Pf = 0.

Control of coronary vascular tone by nitric oxide.

A specific difference-spectrophotometric method was used to measure nitric oxide (NO) release into the coronary effluent perfusate of isolated, constant-flow-perfused guinea pig hearts. Authentic NO applied into the coronary circulation decreased vascular resistance dose dependently and enhanced coronary release of cyclic GMP (cGMP) fivefold. Increasing oxygen tension in aqueous solutions from 150 to 700 mm Hg decreased NO half-life (5.6 seconds) by 32%. During single passage through the intact coronary system, 86% of the infused NO was converted to nitrite ions. Oxidation of NO was more than 30 times faster within the heart than in aqueous solution. Endogenously formed NO was constantly released into the coronary effluent perfusate at a rate of 161 +/- 11 pmol/min. The NO scavenger oxyhemoglobin and methylene blue increased coronary resistance and decreased cGMP release (basal release, 342 +/- 4 fmol/min), whereas superoxide dismutase reduced coronary resistance. L-Arginine (10(-5) M) slightly decreased coronary perfusion pressure and enhanced release of cGMP. NG-Monomethyl L-arginine (10(-4) M) reduced basal release of NO and cGMP by 26% and 31%, respectively, paralleled by a coronary vasoconstriction. Bradykinin in the physiological range from 5 x 10(-11) M to 10(-7) M dilated coronary resistance vessels, which was paralleled by the release of NO and cGMP. Onset of NO release preceded onset of coronary vasodilation in all cases. Upon stimulation with bradykinin, amounts of endogenously formed NO were within the same range as the dose-response curves for exogenously applied NO both for changes in coronary resistance and cGMP release. Acetylcholine (10(-5) M), ATP (10(-5) M), and serotonin (10(-8) M) increased the rate of NO and cGMP release, resulting in coronary vasodilation. Our data suggest the following: 1) NO, the most rapidly acting vasodilator presently known, is metabolized within the heart mainly to nitrite and exhibits a half-life of only 0.1 second; 2) in the unstimulated heart, basal formation of NO may play an important role in setting the resting tone of coronary resistance vessels; 3) the kinetics and quantities of NO formation suggest that NO is causally involved in the bradykinin-induced coronary vasodilation; and 4) amounts of NO formed within the heart stimulated with ATP, acetylcholine, and serotonin are effective for vasodilation.

Role of Adenosine in Catecholamine-Induced Global Coronary Functional Hyperemia in Isolated Guinea Pig Hearts

This study was designed to test the hypothesis that endogenous adenosine participates in the global coronary functional hyperemia accompanying intracoronary infusions of norepinephrine (NE) and isoproterenol (ISO). Intracoronary adenosine deaminase (ADA) was employed to test the hypothesis in isolated, perfused guinea pig hearts. We measured coronary perfusate flow (CPF) at a constant coronary perfusion pressure. Heart rate (HR), left ventricular pressure, and its rate of development were also measured. Global myocardial oxygen consumption (MVO2) and oxygen extraction were calculated, and blood gases and pH were measured routinely in inflow and outflow perfusate samples. In the absence of ADA, NE and ISO increased HR 67 +/- 6 and 106 +/- 11 beats.min-1, left ventricular pressure development 519 +/- 46 and 375 +/- 35 mm Hg.s-1, MVO2 22 +/- 2 and 28 +/- 3 microliters.min-1.g-1, and CPF 1.6 +/- 0.2 and 2.2 +/- 0.2 ml.min-1.g-1, respectively. With constant infusion of ADA (4.5 U.min-1.g-1, a dose which produces no direct effects on cardiac function) for 4 min, similar increments in HR and left ventricular pressure development were achieved with both catecholamines. Corresponding changes in MVO2 (9 +/- 2 and 6 +/- 3 microliters.min-1.g-1) were significantly less than those seen in the absence of ADA. Moreover, CPF did not increase in response to NE and ISO in the presence of ADA. These findings support an important role for adenosine in catecholamine-induced global coronary functional hyperemia in isolated, perfused guinea pig hearts.

Metabolic oxidation of pyruvate and lactate during early myocardial reperfusion.

We have previously described the rates of oxidation for long-chain fatty acids and glucose in stunned myocardium during early reflow after moderately severe regional ischemia. The purpose of these studies was to characterize the rates of pyruvate and lactate oxidation during comparable periods of reflow. In the main protocol, pyruvate oxidation was defined at two conditions of coronary flow and at two levels of fatty acids in the coronary perfusate. Twenty animals were prepared using the extracorporeally perfused, working swine heart model. In five control (group 1) hearts, flow in the left anterior descending coronary artery was maintained at aerobic levels during a 115-minute perfusion trial. In 15 hearts (groups 2 and 3), flow was held at aerobic levels for 30 minutes, reduced acutely by 60% for 45 minutes, and restored again to aerobic levels for the final 40-minute reflow. In the five control hearts and in 10 of the reperfused hearts (group 2), 20% Intralipid (KabiVitrum, Alameda, California) with heparin was infused to raise serum fatty acids to an average of 0.95 +/- 0.08 mumol/ml, whereas in the five remaining nonsupplemented group 3 hearts, serum levels of fatty acids were 0.49 +/- 0.10 mumol/ml. Ischemia in supplemented and nonsupplemented hearts caused a decline in regional mechanical performance (-40 delta % and -39 delta % below aerobic values in active shortening) that failed to recover completely (-16 delta % and -25 delta % below aerobic values in active shortening) during reflow.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of S-adenosylhomocysteine to cardiac adenosine formation

The S-adenosylhomocysteine (SAH) hydrolase inhibitor adenosine dialdehyde was used in isolated guinea pig hearts to determine the contribution of the transmethylation pathway to cardiac adenosine formation. This inhibitor did not alter cardiac hemodynamics but effectively inhibited SAH-hydrolase activity under in vitro and in vivo conditions. In normoxic perfused hearts adenosine dialdehyde (10 μ m) caused tissue levels of SAH to linearly increase at a rate of 160 pmol/g/min over 60 min. At the same time adenosine dialdehyde decreased release of adenosine into the coronary effluent perfusate by 16 pmol/min (34%). Hypoxic perfusion (30% O 2) of guinea-pig hearts increased release of adenosine from 43 to 3700 pmol/min. However, rate of SAH formation in the presence of adenosine dialdehyde was only slightly enhanced from 160 to 200 pmol/g/min and adenosine dialdehyde did not significantly alter the hypoxia induced adenosine release. Since all experiments were performed in the presence of the adenosine deaminase inhibitor EHNA (5 μ m) the results demonstrate: (1) the transmethylation pathway of the heart contributes one third to global cardiac adenosine production under normoxic conditions and provides a constant source of adenosine independent of tissue oxygenation. (2) The majority of SAH-derived adenosine is salvaged most likely via adenosine kinase. (3) The hypoxia induced adenosine production is predominantly derived from enhanced 5′AMP hydrolysis.

Nitric oxide release from the isolated guinea pig heart

Nitric oxide (NO) release from isolated guinea pig hearts into the coronary effluent perfusate was measured with a specific spectrophotometric assay. Nitric oxide was continuously released under basal conditions at a rate of 216 ± 36 pmol/min. Bradykinin (5 × 10 −10−10 −8 M) stimulated the release of nitric oxide in a dose-dependent manner. The start of NO release preceded coronary vasodilation by 5 ± 1 s. Our results suggest that the endogenous formation of nitric oxide is quantitatively sufficient to influence the coronary vascular tone and thus may play a significant role in the regulation of coronary vascular resistance.

Effect of Experimental Cardioplegia Methods on Normal and Hypertrophied Rat Hearts

The purpose of this study was to evaluate whether the addition of verapamil hydrochloride to oxygenated glucose-rich cardioplegic solution would improve myocardial preservation. The Langendorff preparation of the isolated rat heart was used. Groups of normal (WKY) and hypertrophied (SHR) hearts were treated by five different cardioplegic methods and subjected to 90 or 30 minutes of ischemia at 28° to 29°C and reperfusion at 37°C. The following cardioplegic solutions were used: Group A, cold (16°C) Krebs-Henseleit (KH) glucose free only; Group B, KH with KCL (30 mEq/L) (16°C); Group C, same as B with verapamil (10 μM); Group D, perfusion with oxygenated KH solution containing KCL (30 mEq/L) for 15 minutes prior to ischemia; and Group E, same as D with verapamil (10 μM). Recovery of contraction amplitude, ischemic contracture, coronary perfusate volume, the amount of creatine kinase in the coronary perfusate, heart rate, time of revival, O 2 consumption, and ischemic contracture were measured. After 30 minutes of ischemia, we did not find any significant difference among the combinations tested with respect to contraction amplitude recovery. The hearts recovered fully. After 90 minutes of ischemia, we found that the best-protected groups in the normal hearts were Groups D and E. In the hypertrophied hearts, the addition of verapamil to the enhancement solution was harmful. The use of enhancement solution without verapamil prior to ischemia provided the best myocardial protection in the hypertrophied hearts.

Effect of packed cell volume on diastolic coronary artery pressure-flow relations in the dog.

To elucidate the role of the haemorheological properties of the perfusate in the coronary circulation, the diastolic pressure-flow relation was studied in nine open chest heart blocked dogs with minimal vasomotor tone when blood with various packed cell volumes (12-67%) was used as perfusate. An electrical analogue model with proximal resistance R1, capacitance C, distal resistance R2, and the zero flow pressure intercept Pint was derived from the observation of the pressure-flow relation to support the data analysis. The diastolic pressure decay was then determined after the perfusion line had been clamped to calculate stop flow coronary artery pressure (Psf). The stop flow coronary artery pressure decreased in relation to packed cell volume (r = 0.45, p less than 0.01), and the value for the lowest packed cell volume (10-29%) was slightly higher than the great cardiac vein pressure (about 3 mmHg). The zero flow pressure intercept of the steady state pressure-flow relation showed a close correlation with the stop flow coronary artery pressure (r = 0.87, p less than 0.001). The value of R1 + R2, which reflects the inverse of the steady state pressure-flow slope, decreased simultaneously with the packed cell volume (r = 0.62, p less than 0.001). The resistance ratio R2/(R1 + R2) by our model prediction decreased in relation to packed cell volume (r = 0.5, p less than 0.001). The values of stop flow coronary artery pressure, zero flow pressure intercept, and R1 + R2 for the highest packed cell volume (50-69%) were 17.8(1.1) mmHg, 25.1(1.3) mmHg, and 0.48(0.05) mmHg.ml-1.min.100 g-1 respectively, whereas those for the lowest packed cell volume (10-29%) were 13.4(0.8) mmHg, 19.7(1.0) mmHg, and 0.24(0.02) mmHg.ml-1.min.100 g-1. The pressure difference between the stop flow coronary artery pressure and the zero flow pressure intercept may be due to the non-linearity in the pressure-flow relation at a low perfusion pressure. The left ventricular end diastolic pressure and great cardiac vein pressure did not change in relation to the packed cell volume of the coronary perfusate. Thus it is concluded that packed cell volume is one factor determining the high zero flow pressure.

Coronary vasodilation during global myocardial hypoxia: effects of adenosine deaminase

Isolated, perfused guinea pig hearts were infused with intracoronary adenosine deaminase to investigate the contribution of endogenous adenosine to the coronary vasodilation of global myocardial hypoxia. Coronary perfusate pressure was held constant at 70 cmH2O throughout the experiment. We measured retrograde aortic inflow (assumed to equal total antegrade coronary flow) for 3-5 min of hypoxia before and 4 min after initiation of intracoronary adenosine deaminase infusion (4 U.g-1.min-1). In the absence of adenosine deaminase mild global hypoxia increased coronary perfusate flow 60%. In the presence of adenosine deaminase the response was limited to a 5% increment. Myocardial O2 consumption was significantly reduced during hypoxia in the presence of adenosine deaminase. In a second group of hearts, moderate global hypoxia increased coronary perfusate flow 125%. This was limited to a 53% increment in the presence of adenosine deaminase. Adenosine deaminase vehicle had no measurable effect on coronary perfusate flow responses to repeat mild hypoxia in a third group of hearts. We conclude that endogenous adenosine is singularly important in the coronary vasodilation of mild global myocardial hypoxia, but that other regulatory mechanisms might also contribute during moderate hypoxia.

Control of redox potential in oxygenated and anoxic coronary perfusates with N-acetyl cysteine and ascorbic acid: P.S. Rao, N. Rujikarn, J.M. Luber, Jr. Division of Cardiothoracic Surgery, Long Island Jewish Medical Center, New Hyde Park, NY

Control of redox potential in oxygenated and anoxic coronary perfusates with N-acetyl cysteine and ascorbic acid: P.S. Rao, N. Rujikarn, J.M. Luber, Jr. Division of Cardiothoracic Surgery, Long Island Jewish Medical Center, New Hyde Park, NY

Epinephrine-induced renin secretion is not initiated by cardiac adrenoceptors.

Experiments were designed to test the hypothesis that epinephrine may act directly on cardiac or pulmonary adrenoceptors to alter the release of a humoral substance that in turn influences renin secretion. Accordingly, anesthetized dogs were prepared with catheters for infusion of epinephrine at three sites: 1) into the aorta just distal to the left subclavian artery, 2) into the left ventricle, and 3) near the right atrium. Left renal renin secretion rates were determined before, during, and after 30-min infusions of epinephrine at each site in each animal; the order of the infusions was randomized. At epinephrine infusion rates of 15 and 75 ng.kg-1.min-1, epinephrine-induced changes in renin secretion rates were dose dependent but were independent of the site of infusion. These data do not support the hypotheses that either pulmonary or cardiac adrenoceptors are involved in the initiation of epinephrine-induced renin secretion. In additional experiments, an isolated canine heart was perfused with femoral arterial blood from an experimental dog, and the coronary venous effluent was returned to the experimental dog via the femoral vein. Intravenous epinephrine infusion at 50 ng.kg-1.min-1 increased plasma renin activity nearly 1.5-fold. In contrast, plasma renin activity did not increase during infusion of epinephrine at 5 ng.kg-1.min-1 directly into the coronary perfusate of the isolated heart. Coronary perfusate epinephrine concentration was 699 +/- 71 pg/ml (mean +/- SE) during intravenous infusion and was 851 +/- 121 pg/ml during direct infusion of epinephrine into the coronary perfusate. We conclude that cardiac adrenoceptors do not participate in the initiation of epinephrine-induced renin secretion.

Contribution of hemorheological characteristics of coronary perfusate to the coronary artery pressure-flow relationship

Contribution of hemorheological characteristics of coronary perfusate to the coronary artery pressure-flow relationship

Histamine-induced changes in coronary circulation and myocardial oxygen consumption: influences of histamine receptor antagonists.

The effects of histamine and selected H1 and H2 histamine receptor antagonists on cardiac inotropic and chronotropic activity, coronary perfusate flow (CPF), and myocardial oxygen consumption (MVO2) were studied in isolated guinea pig hearts perfused at constant pressure. Data were collected at the end of a 3-min infusion period at steady state. Cardiac performance increased significantly whereas CPF decreased during histamine infusion. MVO2 remained constant owing to a significant increase in myocardial oxygen extraction. Diphenhydramine attenuated the coronary vasoconstriction but potentiated the positive inotropic response. Cimetidine attenuated the inotropic and chronotropic responses but had no effect on coronary vasoconstriction. In combination, the histamine antagonists attenuated the changes in heart rate, contractility, and CPF. The histamine-induced increase in myocardial oxygen extraction was accompanied by a significant increase in MVO2 in the presence of diphenhydramine. The ratio of the change in oxygen extraction to the change in oxygen consumption caused by histamine was significantly increased by diphenhydramine. This compensated for a histamine-induced decrement in the ratio of the change of CPF to the change in oxygen consumption. Cimetidine had no effect on the changes in coronary flow, oxygen consumption, or the above ratios. Thus, histamine causes direct coronary vasoconstriction via an H1 receptor mechanism, cardiac positive inotropy by an H2 receptor mechanism, and cardiac positive chronotropy by combined H1 and H2 mechanisms. In the presence of a histamine-induced decrease in myocardial oxygen supply, increments in oxygen demand are met by increased oxygen extraction.

Effects of halothane on myocardial high-energy phosphate metabolism and intracellular pH utilizing 31P NMR spectroscopy.

Utilizing 31phosphorus nuclear magnetic resonance (NMR) spectroscopy, the authors tested the two hypotheses that the negative inotropic action of halothane is the result of: 1) myocardial intracellular acidosis, and 2) a decrease in myocardial high-energy phosphates. In isolated, paced, Langendorff-perfused rabbit hearts, halothane (1.5 vol %) dissolved in the coronary perfusate produced a 48 +/- 2% decrease (P less than 0.01) in left ventricular developed pressure. In contrast, halothane administration had no significant effect on myocardial intracellular pH (7.18 +/- 0.04 at control vs 7.21 +/- 0.02 during halothane). Halothane exposure decreased (P less than 0.01) the forward rate constant of the creatine kinase reaction by 32 +/- 6%, as measured using saturation transfer NMR, suggesting a decline in the rate of high-energy phosphate metabolism. This was further indicated by a concomitant decrease (P less than 0.05) in myocardial oxygen consumption (20 +/- 5%). During the halothane-induced reduction in left ventricular developed pressure, only small decreases in the myocardial steady state concentrations of phosphocreatine (7 +/- 1%; P less than 0.01) and beta ATP (12 +/- 4%; P less than 0.05), and an increase in Pi (18 +/- 6%; P less than 0.05) were observed. However, similar changes in steady-state high-energy phosphate metabolites were also measured in time-control hearts not exposed to halothane. These results indicate that the negative inotropic action of halothane is not mediated by myocardial intracellular acidosis. Moreover, these findings do not support the concept that the negative inotropic action of halothane is the result of a reduction in myocardial high-energy phosphates.

Pressure-dependent vasoactive effects of histamine in the coronary circulation.

Twenty-one isolated, perfused, spontaneously rhythmic guinea pig hearts (Langendorff preparation) were used to investigate the effects of coronary perfusion pressure (CPP) on the coronary vasoactive response to a continuous infusion of histamine. Heart rate (HR), coronary perfusate flow (CPF), left ventricular pressure, dp/dtmax, oxygen extraction, and myocardial oxygen consumption (MVO2) were measured at constant CPP of 40 (n = 9), 53 (n = 6), and 65 cm H2O (n = 6) in the absence and presence of continuous intracoronary infusion of histamine [0.9 +/- 0.2 microgram/(min X g)]. At 40 cm H2O histamine caused significant coronary vasodilation. At 65 cm H2O histamine caused significant coronary vasoconstriction. At an intermediate pressure of 53 cm H2O histamine had no effect on CPF. At all three pressures HR, left ventricular pressure, dp/dtmax, and oxygen extraction increased significantly in response to histamine. MVO2 was unchanged by histamine at 65 cm H2O (flow was reduced but extraction increased. MVO2 increased modestly but significantly at 53 cm H2O (12% increase; flow unchanged but extraction increased), and increased prominently at 40 cm H2O (50% increase; flow and extraction increased). We conclude that the coronary vascular effects of continuously infused histamine are dependent on the preexisting, steady-state level of CPP in the isolated perfused guinea pig heart.

Factors influencing coronary vascular resistance during hypothermia

Factors influencing total coronary vascular resistance (CVR) during hypothermia were studied in 30 mongrel dogs. Complete isolation of the heart in situ was achieved by transection of all cardiac neural and vascular connections in 15 dogs (denervated, Group I). Cardiac innervation was maintained in the other 15 dogs using systemic normothermic cardiopulmonary bypass (innervated, Group II). The aortic root was perfused with heparinized oxygenated blood at a constant flow rate at variable myocardial temperatures. Electromechanical arrest was achieved using potassium chloride (KCl) (25 meq/liter) added to the coronary perfusate. In each group, 5 dogs were maintained at a flow rate of 10 cc/kg/min without KCI and allowed to beat spontaneously, another 5 at a flow rate of 10 cc/kg/min and arrested with KCl, and the remaining 5 at a flow rate of 5 cc/kg/min with KCl. Total coronary vascular resistance was calculated from aortic root pressure, right atrial pressure, and flow rate and expressed in units per 100 grams of cardiac tissue. At 37°C, resistance was lower in the denervated arrested (1.3 ± 0.2) than in the innervated arrested hearts (2.1 ± 0.2) ( P < 0.001). Preservation of spontaneous electromechanical activity in the innervated hearts resulted in a lower resistance (0.4 ± 0.1) ( P < 0.001). A progressive decrease in myocardial temperature to 15°C resulted in a corresponding decrease in coronary vascular resistance to a plateau value (0.5 to 0.7 U) in all arrested groups. The data suggest that at normothermia, innervation increases vascular tone in the coronary vascular bed, while electromechanical activity decreases it. Hypothermia counteracts neurally mediated vascular tone, paralyzes autoregulatory mechanisms, and results in a significant coronary vasodilatation in the arrested heart.

Role of cellular energy state and adenosine in the regulation of coronary flow during variation in contraction frequency in an isolated perfused heart

Regulation of coronary flow as a function of myocardial energy expenditure was investigated in isolated perfused rat hearts electrically paced at the desired frequencies. The sinoatrial node was excised to lower the endogenous heart rate. The main covariants measured were phosphagen, inorganic phosphate, adenosine, inosine and hypoxanthine concentrations in the tissue, washout of nucleosides and hypoxanthine into the perfusate, oxygen consumption and coronary flow. Oxygen consumption was linearly correlated with heart rate and coronary flow, while the correlation between coronary flow and perfusate adenosine was nonlinear. The adenosine concentrations in the tissue and perfusate showed a mirror image curvilinearity reminiscent of a threshold pattern for adenosine washout. The tissue adenosine content had a negative linear correlation with the adenylate phosphorylation potential (long(ATP/ADP X Pi)). Adenosine output was linearly correlated with free AMP concentration in the tissue, the latter being calculated from the equilibrium of the adenylate kinase reaction. The results confirm the correlation between cellular energy state and coronary flow and support the notion that the mediators between the former and the vascular smooth muscle involve the concentration of free AMP in the tissue, suggesting that the formation of adenosine may be limited by the availability of AMP. The results are in agreement with the hypothesis that adenosine is the diffusible extracellular mediator in the energy-linked regulation of coronary flow.

Contribution of coronary endothelial cells to cardiac adenosine production.

Experiments were performed in isolated non-working guinea pig hearts perfused according to the Langendorff technique (95% O2, 5% CO2), to evaluate the relative contribution of the coronary endothelium to the formation of cardiac adenosine during hypoxia, hypercapnia, and acetylcholine infusion. For this purpose the adenine-nucleotides of the coronary endothelium were prelabeled by perfusion of isolated hearts with 3H-adenosine (10(-8) M) for 35 min. Changes in the relative specific radioactivity (RSA) of adenosine released into the coronary effluent perfusate were used to assess changes in the relative contribution of the coronary endothelium and cardiomyocytes to total cardiac adenosine release. Hypoxic perfusion (15% O2) doubled coronary flow and increased total adenosine release by about two orders of magnitude and in addition, substantially increased the release of 3H-adenosine. The RSA of adenosine, however, was consistently depressed. During hypercapnic acidosis (9% CO2) the increase in coronary flow was associated with only a small and transient rise in cardiac adenosine release, and did not influence the formation of 3H-adenosine. In the unpaced heart, acetylcholine (10(-7) and 2 X 10(-6) M) dose-dependently increased coronary flow and the release of both adenosine and 3H-adenosine. Within the first minute, the RSA of adenosine was increased, but thereafter was decreased relative to control. In the paced heart, the effects of acetylcholine (2 X 10(-6) M) were greatly attenuated. Increasing coronary flow by bradykinin and isosorbide dinitrate or decreasing heart rate by (-)N6-phenylisopropyl-adenosine did not significantly affect effluent perfusate concentration of adenosine or its RSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced mechanical activity of perfused rat heart following morphine or enkephalin peptides administration.

In the isolated and perfused rat heart, the addition of morphine, methionine-enkephalin or leucine-enkephalin to the coronary perfusate, significantly reduces the mechanical activity by negatively affecting both the heart rate and the developed tension. These effects are dose dependent and maximally evident with leucine-enkephalin. Furthermore all the opioids strongly reduce the activity of isoproterenol-stimulated hearts. The suggestion is made that opioid peptides directly influence the cardiac mechanical activity possibly by interacting with membrane-receptor systems.

Prevention of lactate production and myocyte injury in isolated rat hearts perfused with perfluorochemical emulsion

The ability of an oxygenated perfluorocarbon (PFC) emulsion to prevent early signs of myocardial cell stress associated with Krebs-Henseleit (KH) perfusion was evaluated in isolated rat hearts supported in a Langendorff apparatus. Throughout the two-hour perfusion, hearts in both perfusion groups had similar left ventricular pressure and rates of left ventricular pressure development (dP/dt). After 2 h, coronary perfusate flow was 6.6 +/- 1.0 ml/min in the KH group and 2.2 +/- 0.1 ml/min in the PFC group. Oxygen content was 1.5 +/- 0.1 ml/100 ml and 3.4 +/- 0.1 ml/100 ml, in KH and PFC groups, respectively. Perfusate lactate levels rose from zero to 24.0 +/- 8.0 microgram/ml in the KH group and to 10.0 +/- 3.0 micrograms/ml in the PFC group. Reduction in myocardial cell injury and in total calcium content was also observed in hearts perfused with PFC emulsion. At the electron microscopic level, mitochondrial structure was preserved in both normal and injured myocytes of hearts perfused with PFC. We conclude that early signs of anaerobic metabolism are retarded by perfusion with PFC emulsions and that ventricular contractile performance is maintained at approximately one-half coronary perfusate flow in the PFC hearts. The mechanism whereby coronary flow is regulated downward in the PFC perfused hearts remains unanswered.