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Biomedical subjects

W Flameng

Publications and source records attributed to W Flameng.

At least 145 records · Page 8Linked to original sources
PubMed1993

Potentiated state contractions in isolated hearts: effects of ischemia and reperfusion.

To investigate mechanisms underlying the contractile dysfunction during myocardial "stunning," potentiated contractions were studied in Langendorff-perfused rabbit hearts paced at 2.5 Hz. Isovolumetric left ventricular pressure (LVP) and the first derivative of LVP (dP/dt) were measured via a balloon. Potentiated contractions, elicited after 3 s of rest (postrest potentiation, PRP) or with paired pulses (paired-pulse potentiation, PPP) were first characterized in nonischemic conditions. Exposure to 5 nM ryanodine changed PRP into postrest depression [control, 134 +/- 1.7% (SE); ryanodine, 65 +/- 3.4%; n = 5] but did not decrease PPP (control, 125 +/- 7.2%; ryanodine, 141 +/- 14.5%). When sarcolemmal Ca2+ influx was decreased by 0.2-2 microM verapamil, PRP increased (control, 136 +/- 3.7%; 1 microM verapamil, 214 +/- 23.8%; n = 5), whereas PPP was maintained (control, 134 +/- 8.0%; 1 microM verapamil, 154 +/- 11.5%). During ischemia, both PRP and PPP were increased above preischemic values (from 128 +/- 1.9 to 355 +/- 60.4% and from 122 +/- 5.4 to 313 +/- 37.4%, respectively, n = 5). Changes of potentiation of dP/dt were qualitatively similar to those of LVP. On reperfusion, rest potentiation transiently decreased (PRP of dP/dt: 127 +/- 6% preischemia vs. 112 +/- 3% at 2 min postischemia; n = 6). However, PPP increased during the first 20 min of reperfusion (PPP of dP/dt: 184 +/- 22% preischemia vs. 236 +/- 34% postischemia; n = 6). This transient depression of PRP during reperfusion suggests an impairment of sarcoplasmic reticulum function in stunned myocardium, at least during the early phase of reperfusion.

Animals↗
PubMed1993

Adenine nucleotide degradation in ischemic rabbit lung tissue.

The aim of the study was to determine the pathways and site of adenosine triphosphate (ATP) catabolism during lung ischemia, which thus far are largely unknown. For this purpose we used the isolated rabbit lung. Rabbit lungs were flushed in situ with a modified Krebs-Henseleit solution (60 ml/kg), the deflated heart lung blocks were isolated, immersed in saline solution, and stored at 37 degrees C. In group I (normothermic ischemia; n = 6) tissue content of ATP decreased progressively from 9.42 +/- 0.58 mumol/g dry wt to 3.42 +/- 0.24 mumol/g dry wt after 30 min of ischemia and further to 0.51 mumol/g dry weight after 4 h. Hypoxanthine was the major catabolite (92% of the nucleoside and purine base fraction at 4 h ischemia). Adenosine did not accumulate (preischemic 0.08 +/- 0.02 mumol/g dry weight vs. 0.13 +/- 0.01 mumol/g dry weight; P > 0.05). AMP accumulated, but also inosine monophosphate (IMP), which was undetectable before ischemia, increased significantly during ischemia. To determine the breakdown pathway of AMP, 400 microM of the adenosine deaminase inhibitor EHNA was added to the flush solution in group II (n = 6). During ischemia, ATP breakdown was unaltered but adenosine became the major catabolite (2.8 times the concentration of hypoxanthine at 4 h ischemia). By pretreatment of the rabbits with the nucleoside transport inhibitor R 75231 (group III; n = 6) no effect was observed on the concentrations during ischemia of inosine and hypoxanthine and only a minor increase of adenosine was found. Cytochemical localization of nucleoside phosphorylase revealed activity predominantly in the endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1993

Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function.

BACKGROUND: Studies done in potential donors for heart transplantation and in experimental animals have suggested that brain death can have major histopathological and functional effects on the myocardium. METHODS AND RESULTS: We developed experimental models of brain death using dogs to study the hemodynamic and catecholamine changes, the extent of myocardial structural damage, and the recovery potential of donor hearts obtained from brain-dead donors. Brain death was caused by increasing the intracranial pressure (ICP) suddenly or gradually by injecting saline in an epidural Foley catheter. In a first series of experiments, dogs given a sudden rise in ICP (n = 5) showed a hyperdynamic response and a 1,000-fold increase in the level of epinephrine after brain death. Histology revealed 93 +/- 2% of the myocardium to be severely ischemic. Dogs given a gradual rise in ICP (n = 6) showed a lesser hyperdynamic response, almost 200-fold increase in the level of epinephrine after brain death, and mild ischemic damage to the myocardium (23 +/- 1%). In a second series, hearts obtained from brain-dead and non-brain-dead donors were transplanted in recipients, and the weaning and recovery potential were studied. All four recipients with hearts from non-brain-dead donors were weaned with good functional recovery. Also, all four recipients with hearts from brain-dead dogs given a gradual rise in ICP were weaned with only moderate functional recovery. However, only two of four recipients with hearts from donors given a sudden rise in ICP were weaned and showed poor functional recovery. CONCLUSIONS: Our results indicate that a sudden rise in ICP can cause irreversible myocardial damage.

Animals↗
PubMed1993

Recovery of function and adenosine triphosphate metabolism following myocardial ischemia induced in the presence of volatile anesthetics.

Using a normothermic isolated working rabbit heart model, experiments were performed to determine whether exposure to halothane or isoflurane prior to ischemia improved postischemic recovery of myocardial function and the preservation of myocardial high energy phosphates. After 30 min of Langendorff perfusion, hearts were perfused for 30 min in the working mode. Three groups were studied: 1) the blank undergoing no pretreatment during an additional 15 min of working mode; 2) hearts exposed to 1.5% halothane; and 3) hearts exposed to 2.3% isoflurane during the additional 15 min of working mode. Subsequently, all hearts underwent 15 min of global normothermic ischemia, followed by 5 min of Langendorff reperfusion and 15 min of working heart mode using a perfusate devoid of volatile anesthetic. Adenosine triphosphate (ATP) and catabolites were determined after 15 min exposure to volatile anesthetics or blank, after 15 min global ischemia and at the end of the recovery phase. Myocardial function was determined after 30 min of working mode, after exposure to volatile anesthetics, and at the end of the recovery phase. In nonischemic hearts, 15-min treatment with 1.5% halothane or 2.3% isoflurane resulted in a significant decrease in positive LVdP/dt, from 1858 +/- 286 to 1316 +/- 180 mm Hg.s-1 and from 1888 +/- 304 to 1541 +/- 226 mm Hg.s-1, respectively. Coronary flow was increased significantly after isoflurane but not after halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Effects of halothane and isoflurane on collateral dependent myocardium in chronically instrumented dogs.

The effects of moderate systemic hypotension with halothane (HALO) and isoflurane (ISO) on regional myocardial function and perfusion were studied in dogs with chronic coronary artery occlusion. Vasodilator reserve in collateral-dependent (CD) myocardium was quantified in conscious animals by using a dipyridamole challenge test. Blood flow was distributed homogeneously to the normal (Nl) and CD myocardium at rest, but subendocardial perfusion increased only in the Nl area after dipyridamole. HALO and ISO were administered at doses that reduced diastolic arterial pressure to 50 mm Hg. End-tidal concentrations were 1.3 +/- 0.2 vol% for HALO (1.5 minimum alveolar anesthetic concentration) and 1.8 +/- 0.2 vol% for ISO (1.4 minimum alveolar anesthetic concentration), respectively. Global and regional hemodynamic depression were more pronounced with HALO. Systolic wall-thickening fraction decreased both in the Nl (-37%) and CD area (-27%). Myocardial blood flow to Nl and CD myocardium decreased to a comparable extent. ISO predominantly decreased systemic vascular resistance and, when compared to HALO, decreased systolic wall-thickening fraction less in both the Nl (-19%) and CD area (-18%). In addition, regional myocardial perfusion to both Nl and CD myocardium remained virtually unaltered from conscious control conditions. Despite reductions of diastolic blood pressure to 50 mm Hg, neither HALO nor ISO induced ischemic dysfunction in myocardium with diminished vasodilator reserve. Both anesthetics preserved intercoronary as well as transmural blood flow distribution. During HALO, myocardial perfusion was less both in Nl and CD myocardium due to a more pronounced metabolic depression. We conclude that moderate hypotensive doses of ISO and HALO preserve regional myocardial function of collateral-dependent myocardium in dogs with single vessel occlusion and enhanced collateral circulation.

Anesthesia, Inhalation↗
PubMed1993

Catecholamine response to a gradual increase of intracranial pressure.

To determine the catecholamine response to progressive intracranial hypertension, intracranial pressure (ICP) was raised gradually by continuous expansion of an epidural balloon in seven dogs. Hemodynamic parameters, ICP, and cerebral perfusion pressure (CPP) were monitored continuously and serum catecholamine levels began to rise when CPP was in the low-positive range (20 to 30 mm Hg), reaching a peak just after brain death (CPP < or = o mm Hg). There was no correlation between ICP and the catecholamine peak. Compared to control values, the mean increase was 286-fold for epinephrine and 78-fold for norepinephrine. Temporally, the catecholamine peak corresponded well with the observed hemodynamic changes. These results suggest that ischemia in certain parts of the brain stem is responsible for the hemodynamic changes observed in intracranial hypertension (such as the Cushing response), and they show that catecholamines play an important role in these hemodynamic changes.

Animals↗
PubMed1993

Influence of superoxide dismutase on reperfusion injury in donor hearts preserved with Bretschneider-HTK cardioplegic solution.

The ability of superoxide dismutase to prevent reperfusion injury after long-term cold storage of donor hearts was evaluated in canine hearts. Whole blood reperfusion was performed using a 'support animal'. Twelve dog hearts were arrested by a single dose of Bretschneider cardioplegic solution and stored cold (0.5 degrees C) for 24 h. Thereafter they were reperfused for 60 min without (n = 6) or with (n = 6) superoxide dismutase treatment. Myocardial tissue biopsies were taken for determination of high-energy phosphates before explantation, after the preservation period and during reperfusion. Early reperfusion in both groups resulted in an initial recovery of high-energy phosphates and was followed by a decrease during the subsequent reperfusion phase. The latter was associated with the appearance of left ventricular contracture, and cessation of heart beat. Electron microscopic examination of the myocardial tissues after reperfusion revealed a severe reperfusion injury in both groups. It is concluded, that in donor hearts preserved with Bretschneider solution, reperfusion injury cannot be prevented by administration via the perfusate of superoxide dismutase.

Animals↗
PubMed1993

Retrograde versus antegrade delivery of cardioplegic solution in myocardial revascularization. A clinical trial in patients with three-vessel coronary artery disease who underwent myocardial revascularization with extensive use of the internal mammary artery.

The effects of retrograde and antegrade delivery of cardioplegic solution on myocardial function were evaluated and compared in 60 patients who underwent myocardial revascularization. All patients had three-vessel coronary artery disease, and the revascularization was done with extensive use of the internal mammary artery. Seventy-five percent of the distal anastomoses were performed with the internal mammary artery. Myocardial protection consisted of St. Thomas' Hospital cardioplegic solution, topical slushed ice, and systemic hypothermia (28 degrees C). The patients were randomly separated into two groups: group A (n = 30), who received antegrade cardioplegia, and group B (n = 30), who received retrograde cardioplegia. With the exception of the total dose of cardioplegic solution (p = 0.02), there was no significant difference between the two groups that concerned septal myocardial temperature at the moment of asystole and after infusion of the total dose of cardioplegic solution. Cardiac function was assessed before and after the patient was weaned from cardiopulmonary bypass. In the immediate postoperative period there was a significant increase in right atrial pressure of the patients who underwent antegrade cardioplegia. For the other registered parameters there was no significant difference either in the immediate postoperative period or 6 hours later. Release of creatine kinase MB isoenzyme was the same in the two groups. Clinical outcome in terms of mortality, prevalence of perioperative infarction, prevalence of low cardiac output, and rhythm and conduction disturbances was similar in both groups. Technical problems related to cannulation and decannulation of the coronary sinus were not encountered. Multivariate analysis showed that occlusion of the left anterior descending coronary artery (p = 0.012) is an essential contraindication of antegrade delivery of cardioplegic solution. Analysis of the patients with an occlusion of the left anterior descending coronary artery who underwent antegrade (n = 9) and retrograde (n = 10) cardioplegia showed a significant difference in the total dose of cardioplegic solution (p = 0.02) and septal myocardial temperature at the moment of asystole (p = 0.008) and after infusion of the total dose of cardioplegic solution (p = 0.015). The mean arterial systolic blood pressure in the antegrade group was significantly lower than in the retrograde group (p = 0.003). Preservation of the left ventricular stroke work index was significantly better in the retrograde group (namely, 85% of its initial value versus 71% in the antegrade group, p = 0.0116).(ABSTRACT TRUNCATED AT 400 WORDS)

Bicarbonates↗
PubMed1992

Evaluation of myocardial protection by combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia in aorto-coronary bypass grafting.

The concept of pretreatment of the myocardium with a pharmacological agent protecting the cell against ischemic and reperfusion injury is very attractive. Lidoflazine, a calcium overload blocker, predominantly membrane stabilizing, is able to prevent cell damage during ischemic arrest and reperfusion. The purpose of this study was to determine whether the combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia can provide, in clinical practice, better myocardial protection in aorto-coronary bypass grafting than St. Thomas' Hospital cardioplegia alone. As indices for myocardial protection, recovery of cardiac function, enzyme release, and clinical outcome were registered. Ninety-three patients undergoing aorto-coronary bypass surgery were studied. These patients were randomized into two groups in a double blind fashion. Patients in group A (n = 48) received lidoflazine 1 mg/kg intravenously over a period of 20 min before initiation of cardiopulmonary bypass. Group B (n = 45) receiving placebo, acted as a control group. Myocardial protection consisted of intermittent infusion of cold 4 degrees C St. Thomas' Hospital cardioplegia, topical slush ice, and systemic hypothermia (28 degrees C rectal). No significant differences between the two groups were noted in terms of recovery of cardiac function, enzyme release, incidence of myocardial infarction, low cardiac output, rhythm, and conduction disturbances. In conclusion, our data suggest that the combination of intravenous pretreatment with lidoflazine and St. Thomas' Hospital cardioplegia did not provide significant additional myocardial protection in the clinical situation.

Aged↗
PubMed1992

Cardiodynamic effects of dopamine and dobutamine.

On 11 patients undergoing coronary surgery, at the end of the surgical intervention, the inotropic responses to 0.4 and 0.8 microgram x kg-1 x min-1 dopamine and dobutamine given via the aorto-coronary bypass directly into the coronary artery were compared. These dosages correspond to ones 10 times greater applied intravenously. The measurements were made using needle force probes which were implanted into the myocardial offstream area in the left ventricular wall. Bypass flow was measured simultaneously by an electromagnetic flow probe. There is a significant increase in coronary bypass flow induced by both rates of 0.4 and 0.8 microgram x kg-1 x min-1 dobutamine, but there was no significant effect on bypass flow induced by dopamine. Developed myocardial force is raised more by dobutamine medication than by dopamine. However, the rate of contraction increases significantly and relaxation is significantly accelerated by dopamine at both dosages. A significant increase in rate of contraction and relaxation was only induced by the higher dosage of 0.8 microgram x kg-1 x min-1 dobutamine.

Aged↗
PubMed1992

Retrograde coronary sinus cardioplegia in myocardial revascularization: hemodynamic evaluation of the influence on the right-ventricular function.

The problem of the efficacy of right-ventricular protection with retrograde coronary sinus cardioplegia is studied. Sixty patients undergoing myocardial revascularization were prospectively assigned to receive cold St. Thomas' Hospital cardioplegia into the aortic root (30 patients) or retrogradely in the coronary sinus (30 patients). The two groups were similar concerning preoperative and operative data. The hemodynamic recovery postoperatively was good in both groups, the increase of the heart rate, the decrease of the mean aortic pressure and the right-ventricular stroke-work index were not significantly different in the two groups. However, right atrial pressure increased significantly (p less than 0.001) in patients who received cardioplegia anterogradely and decreased, but not significantly, in the retrograde group. The data suggest that the decrease of the right-ventricular stroke-work index in the anterograde group is related to a depressed contractility and in the group with retrograde delivery of cardioplegia to a decreased preload. There were no differences between the groups with respect to clinical outcome. We conclude that retrograde delivery of cardioplegia results in an excellent protection of the right-ventricular function in elective myocardial revascularization.

Adult↗
PubMed1992

Successful transplantation after long-term preservation of dog hearts.

Nucleoside transport inhibition is a new approach to long-term preservation of donor hearts. To evaluate its effectiveness, the following were tested: 1) the effect of nucleoside transport inhibition on high-energy phosphate content after cardioplegic arrest and during long-term cold storage (group I: cardioplegia, control ]n = 18]; group II: cardioplegia plus nucleoside transport inhibitor [n = 18]); 2) the effect of nucleoside transport inhibition on high-energy phosphates and hemodynamic recovery in a modified blood-perfused Langendorff system (group III: 24-h cold storage followed by reperfusion [n = 6]; group IV: addition of nucleoside transport inhibition to cardioplegia but not during reperfusion [n = 6]; group V: addition of nucleoside transport inhibition during reperfusion [n = 6]; group VI: addition of nucleoside transport inhibition to cardioplegia and during reperfusion [n = 6]); and 3) the effect of nucleoside transport inhibition added to cardioplegia and during reperfusion on high-energy phosphate content and outcome after heart transplantation (group VII: no nucleoside transport inhibitor in cardioplegia and during reperfusion [n = 8]; group VIII: addition of nucleoside transport inhibition to cardioplegia and during reperfusion [n = 8]). The following results were obtained: 1) addition of nucleoside transport inhibition prevented high-energy phosphate depletion during cold storage: after 24 h, adenosine triphosphate content in group I was 9.4 +/- 3.1 mumol/g versus 17.7 +/- 3.6 mumol/g dry weight in group II (P less than 0.05); 2) addition of nucleoside transport inhibition to cardioplegia and during reperfusion resulted in greater high-energy phosphate content (adenosine triphosphate in group III was 7.9 +/- 3.5 mumol/g vs. 17.8 +/- 2.8 mumol/g in group VI [P less than 0.05]) and improved hemodynamics upon reperfusion (hearts in group III did not recover, maximum isometric left ventricular pressure development was 1,635 +/- 577 mmHg/sec in group IV, 1,915 +/- 423 mmHg/sec in group V, and 2,437 +/- 201 mmHg/sec in group VI [P less than 0.05, group VI vs. groups IV and V]); and 3) hearts treated with nucleoside transport inhibition in cardioplegia and during reperfusion (group VIII) could be transplanted successfully in contrast to group VII hearts. These data indicate that nucleoside transport inhibition in dogs is highly effective in long-term preservation of donor hearts.

Adenosine↗
PubMed1992

Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake.

To investigate the mechanism underlying postischemic cardiac dysfunction (myocardial stunning), contractility and adenine nucleotide metabolism were studied in three groups of isolated perfused rabbit hearts (control, ischemic, and reperfused), whereas Ca2+ uptake by the sarcoplasmic reticulum (SR) was measured in homogenates obtained from them. The hearts were Langendorff-perfused under constant pressure with Krebs-Henseleit solution at 37 degrees C. Global normothermic ischemia was produced by closing the perfusion line. In the reperfused group, after 15 minutes of ischemia, Krebs-Henseleit solution was perfused for 10 minutes. Developed left ventricular pressure (control, 104 +/- 6.3 mm Hg) and left ventricular dP/dt (2,063 +/- 256.6 mm Hg.sec-1) were significantly decreased in reperfused hearts (left ventricular pressure, 78 +/- 5.9 mm Hg; left ventricular dP/dt, 1,339 +/- 216.3 mm Hg.sec-1). Myocardial ATP content (control, 13.6 +/- 0.98 mumol/g dry wt) decreased during ischemia (4.5 +/- 1.23 mumol/g) but was restored to control level on reperfusion (11.8 +/- 0.68 mumol/g). Maximum velocity of Ca2+ uptake by the SR (Vmax) (control, 49.3 +/- 2.54 nmol.min-1 x mg-1) was significantly depressed by ischemia (36.3 +/- 1.94 nmol.min-1 x mg-1) but was restored to the control value after a 10-minute reperfusion (45.3 +/- 0.79 nmol.min-1 x mg-1). Apparent dissociation constant KCa and the Hill coefficient for Ca2+ uptake were not different between control, ischemia, and reperfusion. To test for the possible role of the SR Ca(2+)-release channel in the effect of ischemia and reperfusion, we measured Ca2+ uptake after incubation of homogenates with 610 microM ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1992

Free polymerized hemoglobin versus hydroxyethyl starch in resuscitation of hypovolemic dogs.

Polymerized bovine hemoglobin (PBH) was compared with hydroxyethyl starch (HES) in a hypovolemic shock model. Eighteen dogs were subjected to hemorrhage; systolic arterial blood pressure was maintained at 40 mm Hg for 30 min (mean blood pressure 37.8 +/- 4.7 [SD] mm Hg). Resuscitation was conducted by infusing their own shed blood (control group) or 6% HES (mol wt 200,000) in 0.9% NaCl (HES group) or PBH (PBH group), both in an equal amount to the shed blood. Directly after infusion, oxygen delivery and consumption returned to prehemorrhage levels in all three groups. In the HES group, the lowered arterial oxygen content was compensated by a 158% increase in cardiac output, in contrast to an increase of 31% and 9%, respectively, in the control and PBH groups. Early recovery from hypovolemic shock with regard to oxygen transport and delivery in the PBH group seemed to be comparable to the control group, without the increase in cardiac output seen with HES infusion.

Animals↗
PubMed1992

Surgery for massive pulmonary embolism.

Pulmonary embolectomies were performed in 30 patients from January 1973 until December 1991 in the University Hospital of Leuven. There was an 80% hospital survival. The late follow-up showed no recurrent pulmonary emboli. The preoperative haemodynamic status was the most important predictor for survival. Patients, under cardiopulmonary resuscitation or in profound cardiogenic shock before surgery, had a survival of only 50% while all other patients survived. Angiography, performed in only 23% of the cases, remained the most important diagnostic tool until the advent of transthoracic and transoesophageal echocardiography. Thrombolysis is an acceptable alternative in the stable patient, but pulmonary embolectomy is life-saving in the haemodynamically unstable patient and when thrombolysis is contraindicated.

Adult↗
PubMed1992

Nucleoside transport inhibition mediates lidoflazine-induced cardioprotection during intermittent aortic crossclamping.

The effects of pretreatment with the nucleoside transport inhibitor lidoflazine on repeated ischemia-reperfusion injury induced by normothermic intermittent aortic crossclamping were studied in canine hearts. Eighteen mongrel dogs were allocated to three groups: placebo (n = 6), lidoflazine (1 mg/kg) (n = 6), and lidoflazine (1 mg/kg) plus the adenosine receptor blocker aminophylline (7 mg/kg) (n = 6). Pretreatment was performed intravenously during 15 minutes before extracorporeal circulation. All hearts were subjected to four intervals of 15 minutes of global ischemia each followed by 10 minutes of reperfusion. After weaning from extracorporeal circulation, functional recovery was followed for 1 hour. In the lidoflazine group, myocardial adenosine content (0.25 +/- 0.06 mumol/gm dry weight) was 3.5 times higher than that in the control group (0.07 +/- 0.03 mumol/gm dry weight; p < 0.05) at the end of the last aortic crossclamping. The release of adenosine from the myocardium during each reperfusion period was significantly higher than that in the control group (p < 0.05). Myocardial extraction of lactate was normalized at every reperfusion interval in the lidoflazine group but not in the control group (p < 0.05). In the lidoflazine group functional recovery was significantly better than that in the control group. Positive rate of rise of pressure, negative rate of rise of pressure, and cardiac output recovered to, respectively, 150% +/- 19%, 82% +/- 8%, and 131% +/- 15% in the lidoflazine group versus, respectively, 37% +/- 9%, 23% +/- 7%, and 29% +/- 8% in the control group (p < 0.001) at 1 hour after extracorporeal circulation. When the adenosine receptor blocker aminophylline was administered in association with lidoflazine, protection dropped significantly: positive and negative rate of rise of pressure and cardiac output were, respectively, 58% +/- 8%, 46% +/- 9%, and 67% +/- 16% at 1 hour after extracorporeal circulation (p < 0.05 versus lidoflazine alone). These results suggest that the cardioprotective effects of lidoflazine are at least in part mediated by adenosine receptor stimulation via nucleoside transport inhibition-induced accumulation of endogenous adenosine in the myocardium.

Adenosine↗
PubMed1992

Effects of nucleoside transport inhibition on long-term ex vivo preservation of canine hearts.

The effect of nucleoside transport inhibition on 24-hour preservation of canine hearts was studied in 36 hearts arrested either with a cold hyperkalemic cardioplegic solution without (group I) or with supplementation of a specific nucleoside transport inhibitor (R75231, 1 mg/L) (groups II and III). The hearts were excised and stored for 24 hours at 0.5 degrees C. Then they were reperfused for 3 hours with use of a closed perfusion system primed with normal blood (groups I and II) or with blood supplemented with the same nucleoside transport inhibitor (0.32 mg/L) (group III). Serial biopsy specimens for determination of myocardial purines were taken. Creatine kinase and heat-stable lactate dehydrogenase release from the myocardium were examined during reperfusion. Recovery of function was studied during reperfusion by measurement of isometric contraction in a fluid-filled intraventricular balloon. After 24 hours of preservation, without the use of the drug, myocardial inosine and hypoxanthine accumulated to, respectively, 4.05 +/- 1.18 and 0.28 +/- 0.08 mumol/gm dry weight. In the drug-treated groups (II and III pooled), significantly less inosine and hypoxanthine accumulated (1.68 +/- 0.33 and 0.05 +/- 0.02 mumol/gm dry weight, respectively) (p < 0.05 versus group I). Upon reperfusion, intramyocardial adenosine was lost in the control hearts and maintained in the drug-treated hearts. Hypoxanthine accumulated significantly (p < 0.05) during reperfusion in group I (1.08 +/- 0.43 versus 0.16 +/- 0.13 in group II and 0.03 +/- 0.03 mumol/gm dry weight in group III). The rate of creatine kinase and heat-stable lactate dehydrogenase release was significantly lower (p < 0.05) in group III (that is, pretreatment and posttreatment with the drug) than in the control group. Functional recovery of hearts in group III was superior to that in group II (p < 0.05), while hearts in group I showed no recovery at all. We conclude that nucleoside transport inhibition improves long-term preservation of the heart and that the mechanism of this protection may be related to an increase in endogenous adenosine and reduction of myocardial hypoxanthine content.

Adenine Nucleotides↗