Biomedical subjects

W Flameng

Publications and source records attributed to W Flameng.

At least 163 records · Page 9Linked to original sources

PubMed1992

Degradation of myocardial high-energy phosphates during twenty-four hours of cold storage. Effects of cardioplegic versus noncardioplegic arrest.

Purine nucleotide catabolism was examined during 24 hours of cold (0.5 degree C) storage of human transplant recipient hearts, baboon hearts, and dog hearts. The hearts were excised either after cold hyperkalemic cardioplegic arrest or after simple hypothermic arrest (25 degrees C). In human myocardium, hypothermia alone preserved the adenosine triphosphate pool markedly. Even after 24 hours of cold storage, adenosine triphosphate was still 9.5 +/- 2.5 mumol/gm dry weight (58% of the preischemic value). The major fraction of catabolites remained nucleotides: adenosine triphosphate plus adenosine diphosphate plus adenosine monophosphate decreased only from 99% +/- 1% (preischemic value) to 80% +/- 13% of the total purine content. The remaining catabolites were mainly nucleosides (adenosine 0.2% +/- 0.1% and inosine 19% +/- 13% of the total purine content). Cardioplegic arrest before cold storage did not change the pattern of purine nucleotide catabolism in any respect (p greater than 0.05). In baboon myocardium, hypothermia alone preserved the adenosine triphosphate content somewhat less than in human myocardium. Adenosine triphosphate content after 24 hours was 5.2 +/- 1.6 mumol/gm dry weight (40% of the preischemic value). The catabolism of adenosine triphosphate, however, did not proceed far beyond the level of adenosine monophosphate, so that the sum of nucleotides remained the same as in human hearts. Adenosine was 0.2% +/- 0.3% and inosine 17% +/- 4% of the total sum of purines. Also in the baboon heart, cardioplegia did not influence the pattern of catabolism significantly (p greater than 0.05). In the dog myocardium, hypothermia alone did not protect against severe catabolism of adenosine triphosphate. The adenosine triphosphate content at 24 hours of storage was 3.5 +/- 2.5 mumol/g dry weight (25% of the preischemic value). Catabolism of adenosine triphosphate proceeded far beyond the level of the nucleotides (63% +/- 17% of the total sum of purines), resulting in an accumulation of adenosine and inosine (5% +/- 4% and 30% +/- 13% of the total sum of purines) and even of hypoxanthine (1% +/- 1% of the total sum of purines). In the dog heart cardioplegic arrest inhibited adenosine triphosphate catabolism considerably. Adenosine triphosphate content at 24 hours was 8.1 +/- 1.8 mumol/gm dry weight (56% of the preischemic value); 83% +/- 5% of the total purine content remained present as nucleotides, and the nucleoside content was reduced to 2% +/- 3% for adenosine and 11% +/- 6% for inosine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗

PubMed1991

31P-NMR study of cardiac preservation: St. Thomas' Hospital cardioplegic solution versus UW preservation solution.

Ex vivo cardiac preservation was evaluated by measuring the catabolism of high-energy phosphate (ATP and creatine phosphate, CrP) using 31P-NMR spectroscopy. After cardioplegic arrest St. Thomas' Hospital cardioplegic solution (group A), and University of Wisconsin (UW) preservation solution (group B) were tested. The hearts were mounted in the 4.7 T horizontal bore magnet of the NMR spectrometer and were continuously perfused with the test solution under 25 cm H2O pressure for 6 h at 10 degrees C. Peak heights of the beta-phosphate of ATP and CrP were measured and expressed as percentages of the initial value. For both group A and group B. ATP declined less rapidly during preservation than CrP. In group A, ATP remained constant for 60 min while CrP decreased from the onset of preservation. After 6 h of preservation 28.3% of ATP and 24.5% of CrP remained (group A). On the other hand, in group B, levels of both ATP and CrP remained much more stable: CrP did not decrease during the first 3 h of preservation, while ATP started to decrease after 5 h. At the end of preservation 76.1% of ATP and 71.5% of CrP were still present. We conclude that UW solution is superior to St. Thomas' Hospital solution for the preservation of high-energy phosphates during 6 h cardiac preservation with continuous hypothermic low-flow perfusion.

Adenosine↗

PubMed1991

Cardioprotective effects of nucleoside transport inhibition in rabbit hearts.

The cardioprotective effects of a nucleoside transport inhibitor, R75231, were investigated in the isolated rabbit heart. The hearts were subjected to 20 minutes of global normothermic ischemia followed by reperfusion. Before ischemia either solvent (group 1), 5 mumol/L of adenosine (group 2), or 0.64 mg/L R75231 (group 3) was added to the perfusate. Preischemic hemodynamics were not changed by treatment, except for an increase in coronary flow in the adenosine group (126% of control; p less than 0.05). Upon reperfusion, coronary flow was depressed in the controls (72% of the preischemic control values), increased in the adenosine group (113%) and unchanged in the R75231 group (89%). Functional recovery was significantly better in the adenosine group as well as in the R75231 group as compared with the controls (p less than 0.05). Cardiac output was 74% of the preischemic control value in the R75231 group, 67% in the adenosine group, and only 38% in the controls. Analysis of the coronary effluent after reperfusion showed a significant inhibition of rapid release of purines and a reverse of the adenosine/inosine ratio in the R75231 group as compared with the others. We conclude that R75231 has a cardioprotective effect that is probably related to accumulation of endogenous adenosine.

Adenosine↗

PubMed1991

Mitochondrial function in myocardial stunning.

Mitochondrial respiration parameters were studied in mitochondria isolated from normal, ischemic and post-ischemic rabbit hearts. Mitochondrial function was related to tissue content of high energy phosphates (HEP) and cardiac function in the isolated working rabbit heart preparation. It was found that after 10 and 20 mins of global normothermic ischemia followed by 20 mins of Langendorff reperfusion, mitochondrial function and HEP content of the myocardium were not significantly diminished. Myocardial creatine phosphate even showed a significant overshoot as compared to the pre-ischemic condition. When these hearts were allowed to perform work, recovery of cardiac function was incomplete while mitochondrial function and HEP content remained in the normal range. Prolonged ischemia (30 mins) resulted in a significant depression of mitochondrial function and myocardial ATP content during and after ischemia. Recovery of contractile function was severely depressed. These results show that impaired cardiac function after a mild ischemic insult (myocardial stunning) can be associated with near normal mitochondrial function and HEP contents.

Adenosine Triphosphate↗

PubMed1991

The return of clinically evident ischemia after coronary artery bypass grafting.

Although survival after coronary artery bypass grafting (CABG) is the most serious outcome information, the quality of life in living patients is largely determined by the freedom from ischemic events. The return of angina, acute myocardial infarct and sudden death were studied in a large (n = 5880) population of patients undergoing CABG between 1971 and 1987. The freedom from angina pectoris was 95%, 83% and 63% at 1, 5 and 10 years, respectively, after surgery. Early return of angina was related to both procedure incremental risk factors (incomplete revascularization and non-use of the internal mammary (thoracic) artery (IMA) as a conduit) and patient incremental risk factors (aggressiveness of the atherosclerotic process and severity of preCABG symptoms). Late angina return was related to patient risk factors including coexisting factors (hyperlipidemia and hypertension), preCABG symptom severity and gender (female). The freedom from an acute fatal or non-fatal postCABG myocardial infarct was 99%, 96% and 85% at 1, 5 and 10 years after surgery. The incremental risk factors for early infarction were related to incomplete revascularization, but late infarction was related to lipid levels, coexisting diseases (diabetes, positive family history) and non-use of IMA to LAD. The freedom from sudden death was 99.8%, 99% and 97% at 1, 5 and 10 years, respectively, after surgery. The incremental risk factors were dominated by the severity of the left ventricular dysfunction. The freedom from any ischemic event (any of the previous three) was 93%, 79% and 54% at 1, 5 and 10 years, respectively, after surgery. The incremental risk factors included all those cited above for the specific components. Patient-specific predictions validate the influences of these risk factors. They demonstrate that unlike the profound influence of the use of the IMA on survival, there is little benefit of the use of the IMA on return of ischemic events over and above the effect of revascularization per se. The study demonstrates that most patients will experience return of ischemic symptoms within a period of 15-20 years after surgery, but that this is most likely to be return of angina and rarely sudden death.

Adult↗

PubMed1991

Effect of superoxide dismutase on infarct size and postischemic recovery of myocardial contractility and metabolism in dogs.

The effects of superoxide dismutase treatment on infarct size, postischemic recovery of contractile function and tissue content of high energy phosphates were examined in a canine model of myocardial ischemia and reperfusion. Ischemia was induced by thrombotic occlusion of a coronary artery and reperfusion was achieved by intravenous thrombolysis. Average duration of ischemia was 90 min. Fifty closed chest anesthetized dogs were randomized to receive either superoxide dismutase (34,000 IU/min intravenously) or placebo, starting approximately 30 min before and continuing for 30 min into the reperfusion phase. Left ventricular ejection fraction and regional segmental shortening of the postischemic area were calculated from contrast angiograms after 4 h, 48 h and 1 week of reperfusion. Tissue content of high energy phosphates was determined from transmural biopsy after 4 h and 1 week. Infarct size was measured by planimetry of dye-stained heart slices. In the superoxide dismutase and placebo-treated groups, respectively, the mortality rate was 25% and 16%, collateral flow 20 +/- 10 and 23 +/- 18 ml/min per 100 g, area at risk 25 +/- 6% and 26 +/- 7% of the left ventricle and infarct size 28 +/- 19% and 36 +/- 27% of the area at risk. Multiple regression analysis failed to show any beneficial effect of superoxide dismutase treatment on infarct size. Left ventricular ejection fraction, regional segmental shortening of the postischemic area and tissue content of high energy phosphates recovered to a similar extent and at a similar rate in both treated and placebo groups up to 1 week after reperfusion. Thus, in this model of coronary occlusion and reperfusion superoxide dismutase treatment is of no benefit.

Adenosine Triphosphate↗

PubMed1991

Quantitative assessment of the effects of 'inodilators' on the myocardium in patients without primary cardiac insufficiency after coronary surgery: Part I--Amrinone.

The positive inotropic and peripheral vasodilating effect of amrinone has been measured in 20 patients without manifest cardiac insufficiency during the early (8-18 h postoperative) and late (18-48 h postoperative) recovery phase after coronary surgery. On conclusion of the surgical intervention first the aortocoronary bypass flow was compared during dobutamine and amrinone administration. It increased by 88% with amrinone and by 19% with dobutamine. Then a needle force probe was implanted in the myocardium. Directly measured local myocardial force increased not significantly by 3.5% after the first and by 5.1% after the second bolus injection of 2 mg/kg amrinone. The rate of myocardial contraction increased by 18.7% and 12%. The rate of relaxation decreased by 5.3% after the first and increased by 15% after the second injection. Mean pulmonary arterial pressure fell from 18.5 to 15.5 mmHg and from 19.7 to 17 mmHg. Cardiac output increased by 23% after the first and by 20% after the second injection. Heart rate rose from 88 to 99 bpm and from 86 to 94 bpm. Total peripheral resistance fell from 1,035 to 706 dyn*s*cm-5 and from 1,036 to 819 dyn*s*cm-5. The systolic arterial pressure fell from 132 to 116 mmHg after the first injection and did not change after the second injection. Amrinone was found to be a powerful peripheral vasodilator with a mild positive inotropic action. The variations in the effects between the early and late recovery phases mainly reflect a progressive haemodynamic stabilization with a decreasing tendency toward hypotensive disregulation. Careful consideration has to be paid to a properly balanced filling of the vascular system before administering amrinone.

Adult↗

PubMed1991

Quantitative assessment of the effects of 'inodilators' on the myocardium in patients without primary cardiac insufficiency after coronary surgery: Part II--Enoximone.

Twelve patients undergoing routine coronary artery surgery received a bolus injection of 1.5 mg/kg enoximone between 8 and 18 hours and again between 18 and 48 hours after operation. No patient showed clinically manifest myocardial heart failure. The haemodynamic and cardiodynamic response to enoximone was quantified over a 30 minutes period following injection. Local myocardial developed force increased by 24 +/- 7% after the first and by 12 +/- 6% after the second injection. The rate of myocardial contraction increased by 50 +/- 14% and 15 +/- 10%, respectively, and relaxation increased by 35 +/- 14% and 22 +/- 19%. There was a decrease in total peripheral resistance of 38.8 and 42.9%, and an increase in heart rate of 11 and 15%. The mean arterial pressure showed small reductions from 73 (+/- 3.7) to 67 (+/- 2.6) mmHg for the first dose and from 83 (+/- 3.1) to 78.4 (+/- 2.8) mmHg for the second. Central venous and pulmonary artery pressures were essentially unaltered. The substantial positive inotropic effect of enoximone has been shown to match its peripheral vasodilatory activity, so that in the normovolaemic patient there is a clinically insignificant small fall in mean arterial pressure.

Aged↗

PubMed1991

Effects of hypothermic ischemia on purine catabolism in canine, primate, and human myocardium.

After hypothermic cardiac arrest, creatine phosphate (CrP) and adenine nucleotide catabolism was compared in myocardium from dogs (n = 7), baboons (n = 5), and man (n = 7; patients undergoing cardiac transplantation) during cold (0.5 degree C) storage for up to 24 hours. Although hypothermia delayed the catabolism in dog myocardium it still remained very extensive. CrP dropped to virtually nil and ATP fell to below 15% of the total purines within 6 hours. The majority of the adenine nucleotides was broken down to adenosine (ADO; 32% of total purines) and inosine (INO; 21%). Apart from the delay (7 to 9-fold), hypothermia also reversed the ratio between ADO and INO when compared to normothermia, suggesting a profound effect of temperature on the nucleoside transporter. In human myocardium even after 12 hours of hypothermia ATP still contributed more than 60% to the total purines. Concomitantly, nucleoside formation proceeded slowly with almost no intermediate ADO. Under similar conditions, the catabolism of ATP in baboon myocardium occurred at a higher rate than in man but still far below canine metabolism. Irrespective of the relatively higher fall in ATP, ADP and AMP accumulated more in baboon myocardium indicating a limited dephosphorylation of the nucleotides. Only in the baboon myocardium did inosine monophosphate increase above the detection limits. In none of the species did purine catabolism proceed beyond hypoxanthine and even this could hardly be detected in the primates. It is concluded that considerable species differences do exist in the rate as well as in the pattern of nucleotide catabolism even during storage of the myocardium at low temperature.

Adenine Nucleotides↗

PubMed1991

Evaluation of factors influencing myocardial infarct size in unconscious dogs.

STUDY OBJECTIVE: The aim was to evaluate the factors determining myocardial infarct size in unconscious dogs. DESIGN: In anaesthetised open chest dogs, the left anterior descending coronary artery was occluded either by ligation or by thrombosis for different time periods (1.5 h, 4 h, 24 h), with or without reperfusion. Haemodynamic variables were recorded throughout the experiment. Radioactive microspheres (15 microns) were injected at the end of the ischaemic period to measure regional myocardial blood flow. Infarct size and area at risk were determined by the Evans blue triphenyltetrazolium staining technique followed by planimetry. SUBJECTS: Mongrel dogs of either sex (n = 16-42 per experiment), weight 18-25 kg, were used. MEASUREMENTS AND MAIN RESULTS: A large interindividual variability in infarct size was observed after occlusion of the left anterior descending coronary artery at a standardised location for a well defined period. An examination of the factors responsible for this variability was carried out in order to develop a statistical model which would make it possible to predict infarct size. Using multiple regression analysis, it was found that in most protocols (except 90 min thrombosis) more than 85% of the variability in infarct size could be explained by the size of the area at risk and the amount of collateral flow. Thus, knowing the area at risk and the collateral flow, a fairly accurate prediction can be made of the size of the infarct that the dog will develop after a defined occlusion period. Furthermore, it was found that the infarct size increased with duration of occlusion, while duration of reperfusion had no effect. In the 90 min occlusion group thrombosis induced a larger final infarct than ligature. CONCLUSIONS: A correction for baseline variables is necessary in order to compare infarct size between experimental groups. The usefulness of this procedure is shown by an example of an experimental intervention, i.e., R 56,865, a drug with known cardioprotective effects.

Animals↗

PubMed1991

Coronary artery thrombosis and thrombolysis in baboons: the effect of atenolol treatment on myocardial infarct size.

The effect of the beta-blocker atenolol on experimental infarct size was studied in a non-human primate model. In 12 baboons thrombosis of the left anterior descending coronary artery (LAD) was induced and atenolol (0.1 to 0.2 mg.kg-1 intravenously, sufficient to lower the heart rate by 20%) was administered 10 min after the onset of ischaemia in six animals, whereas the others received placebo. Thrombolysis was induced 60 min after the onset of ischaemia by intravenous injection of rtPA (12 micrograms.kg-1.min-1) in all animals. Heart rate dropped significantly after atenolol injection (128 +/- 9 beats.min-1 versus 163 +/- 15 beats.min-1, P less than 0.001) and was also lower than in the control group (128 +/- 9 beats.min-1 versus 158 +/- 22 beats.min-1, P less than 0.05). Blood pressure remained unchanged after atenolol treatment. As compared to the control group, atenolol limited infarct size, expressed as a percentage of left ventricular mass (4.6 +/- 1.9% versus 7.9 +/- 1.3%, P less than 0.05) or as a percentage of the perfusion area (26 +/- 8% versus 43 +/- 8%, P less than 0.05).

Animals↗

PubMed1991

[Comparison of new cardiac agents using differential therapeutic criteria].

Positive inotropism, reduction in preload, and reduction in afterload induced by any cardiacum are not exactly quantified in humans, nor are the patients classified as to their respective requirements. Also, any of these drug activities change with the patient's instantaneous cardiac and hemodynamic functional state. One reason for incomplete knowledge is a shortage of methods which allow to assess the inotropic state of the myocardium. In 17 patients, age range 56-76 years (two females, 15 male), undergoing routine coronary surgery, informed consent was obtained for implantation of a needle transducer for measurement of wall force. At the end of coronary surgery, developed myocardial force and aorto-coronary bypass flow were measured electromagnetically. After control measurements, 0.03, 0.06 and 0.1 mg/kg enoximone were injected slowly (3 min per dose) into the aorto-coronary bypass. Eight to 18 h after surgery, and again 18-48 h after surgery, the following measurements were made, first as a control, and then after 1.5 mg/kg enoximone i.v.: aortic pressure (AoP), central venous pressure (CVP) and pulmonary artery pressure (PAP), cardiac output (CO), and heart rate (HR). Peripheral vascular resistance (TPR) was calculated. Developed force and its derivatives were recorded continuously. Immediately after recovery from cardioplegia a 0.19 mg/kg dose of enoximone injected over 9 min into the aorto-coronary bypass induced an increase in bypass flow of 64 +/- 30%. Mean arterial pressure (MAP) showed a fall 5 min after enoximon injection on both occasions. The values were 73 (+/- 3.7) to 67 (+/- 2.6) mmHg, and 83 (+/- 3.1) to 78 (+/- 2.8) mmHg, respectively. The increase obtained in cardiac output (CO) 6.0 (+/- 0.4) to 7.4 (+/- 0.7) l.min-1, and 6.2 (+/- 0.7) to 8.5 (+/- 1.3) l.min-1 was significant at 5 min and remained so at 30 min on both occasions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Effects of beta-adrenoceptor antagonists on cardiac function in ischemic-reperfused myocardium of the isolated working rabbit heart.

The effects of beta-adrenoceptor antagonists (dl-nebivolol, atenolol and propranolol) and of 1-nebivolol on cardiodynamics and mitochondrial oxidative phosphorylation were studied in the isolated working rabbit heart subjected to normothermic global ischemia, followed, in some cases, by reperfusion. The hearts were pretreated with the different drugs (0.32 mg/l) 30 min before the start of ischemia, dl-Nebivolol and propranolol provided protection for both cardiodynamic and mitochondrial functions, as did l-nebivolol, which lacks beta-adrenoceptor blocking properties, while atenolol failed to protect mechanical activity and cardiac mitochondria against the effects of ischemia and post-ischemic reperfusion. Catecholamine depletion with reserpine did not have a beneficial effect on the recovery of cardiodynamic and mitochondrial function during post-ischemic reperfusion. It is concluded that the beneficial effects of beta-blockers on the ischemic and reperfused myocardium can not be explained by a specific beta-blocking action alone.

Adrenergic beta-Antagonists↗

PubMed1990

Effects of left ventricular assist for cardiogenic shock on cardiac function and organ blood flow distribution.

Organ blood flow distribution was studied in dogs subjected to a left ventricular assist device (LVAD). In normal hearts (group 1), left ventricular work was reduced by 25% when 35% of cardiac output was performed by the LVAD. Organ perfusion, measured with tracer microspheres, remained normal or slightly increased. After induction of cardiogenic shock (group 2), perfusion deteriorated in all organs, but first in the brain, kidney, and intestinum. All animals died within 1 hour. When maximal inotropic support was administered after shock (group 3), hemodynamics improved but perfusion to most organs decreased progressively and 83% of animals died within 2 hours. When the LVAD was inserted after shock but without inotropic support (group 4), perfusion of all organs became normal during LVAD except for kidney flow, which remained severely depressed (56% of preshock value). After LVAD insertion, hemodynamics did not recover completely, and 33% of the animals died within 3 hours. When use of the LVAD was combined with 5 micrograms.kg-1.min-1 of dopamine after shock (group 5), organ blood flow distribution became normal during and after LVAD use except for renal flow, which was significantly impaired (83% of preshock value). Hemodynamics recovered after LVAD use, and all animals survived in this group. We conclude that use of the LVAD combined with low-dose positive inotropic support can prevent deterioration of organ perfusion after cardiogenic shock except for kidney.

Animals↗

PubMed1990

Internal mammary artery: methods of use and their effect on survival after coronary bypass surgery.

Hazard analysis of total and cardiac mortality after isolated primary coronary artery surgery was performed using univariate and multivariate methods with special emphasis on the importance of the use and method of use of the internal mammary artery (IMA) as a bypass graft. The clinical data of 5880 consecutive patients were studied. The sum of the real follow-up periods studied was 27,948 years. The hazard of total and cardiac mortality could be defined in three-phase parametric models with an early, a constant and a late phase. The total survival was 82% +/- 1% at 10 years and 59% +/- 3.6% at 15 years. The construction of a single IMA distal graft (using left or right IMA) had a positive influence on the hazard (P = 0.0004) in the late phase after surgery with a high estimate (-1.6). The cardiac survival was 89% +/- 0.8% at 10 years and 74% +/- 3.5% at 15 years. The use of the left IMA had a positive influence (P = 0.001) in the late phase after surgery with a very high estimate (-2.3). The generated simulation of the total survival of a median patient with an IMA graft is 97% at 5 years and 94% at 10 years; for a median patient without an IMA graft, it is 97% at 5 years and 88% at 10 years. If a patient has other risk factors reducing his life expectancy, the influence can be dissipated because of lower survival rates at 5 years after surgery, when the effect of the IMA becomes most apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Belgium↗

PubMed1990

Reperfusion injury after 24 hours cold storage of donor hearts. Possible role of leukocyte activation.

The role of neutrophils on the development of reperfusion injury was evaluated in canine hearts. Reperfusion was performed with a closed reperfusion system. 18 dog hearts were arrested by a single dose of National Institute of Health cardioplegia and stored cold (0.5 degrees C) for 24 hours. Thereafter they were randomly attached to one of the following groups. Group I: reperfusion with whole blood (n = 6), group II: reperfusion with low-leukocyte blood (n = 6), group III: reperfusion with low-leukocyte blood plus phenyl-isopropyl adenosine (PIA) (n = 6). Hearts in group I showed an increase of high energy phosphates (HEP) within the first 30 minutes, and a significant decrease during the subsequent 30 minutes. Concomitantly the initially soft hearts turned into stone hearts. In group II and III a significant increase of HEP was seen during the entire reperfusion. After 60 minutes of reperfusion myocardial ATP levels in group III were significantly higher than in group I. All hearts in group III were soft after reperfusion. It is concluded that reperfusion injury appears to be dependent upon the presence and activation of neutrophils, which can be partially prevented by reperfusion with low-leukocyte blood and more so by the simultaneous administration of PIA.

Animals↗

PubMed1990

Evidence for decreased coronary flow reserve in viable postischemic myocardium.

To try to unravel the complexity and heterogeneity of the "no-reflow" phenomenon and its underlying mechanisms, we studied tissue perfusion in reperfused heart muscle by using tracer microspheres in an anesthetized dog model of 90-minute coronary occlusion followed by reperfusion for 2 1/2 hours, 24 hours, or 1 week. Regional myocardial blood flow was determined both in basal flow conditions and during reactive hyperemia. The effect of intracoronary adenosine administration was examined, and the ultrastructure of postischemic myocardium was analyzed. In viable reperfused tissue (as delineated by triphenyltetrazolium chloride staining), reflow in basal conditions is unimpaired. Coronary flow reserve (as approximated by peak reactive hyperemic flow) is intact at the start of reperfusion, decreases by more than half after 2 1/2 hours, and recovers completely within 1 week. This impairment of coronary reserve can be relieved by intracoronary adenosine administration. On ultrastructural examination, the capillaries are patent. On the other hand, in irreversibly damaged myocardium, both the basal reflow impairment and the decrease in coronary flow reserve are severe and permanent. Coronary flow reserve is already decreased at the start of reperfusion, and the pharmacological intervention has no beneficial effect. Ultrastructurally, extracellular and intracellular edema invariably are present, whereas the vascular endothelium is damaged and the capillaries are packed with red blood cells. We conclude that the no-reflow phenomenon (i.e., mechanical obstruction to blood flow) is limited to infarcted tissue. In viable myocardium, however, coronary flow reserve is transiently diminished, probably because of washout and subsequent insufficient availability of the chemical mediator adenosine after breakdown and slow recovery of the precursor ATP pool.

Adenosine↗

PubMed1990

Cardioprotective effects of carnitine in extensive aortocoronary bypass grafting: a double-blind, randomized, placebo-controlled clinical trial.

The cardioprotective effects of carnitine were tested in patients undergoing multiple aortocoronary bypass grafting. Intermittent aortic cross-clamping at 28 degrees C was used. Mean total cross-clamping time was 30 +/- 11 min. Patients were randomized into three groups: a control group receiving placebo (group 1), a group pretreated with 3 g carnitine intravenously before cardiopulmonary bypass (CPB) (group 2), and a group pretreated with 6 g carnitine intravenously (group 3). The markers of myocardial ischemia included levels of adenosine triphosphate, its catabolites, and creatine phosphate in transmural left ventricular biopsy specimens taken at the beginning and end of CPB, as well as hemodynamic recovery during weaning from CPB and for the next 24 h. The intravenous infusion of carnitine (3 or 6 g) had no hemodynamic effect. At the end of CPB myocardial tissue levels of adenosine triphosphate and creatine phosphate did not differ significantly among the groups (P greater than 0.05). Recovery of cardiac function during weaning from CPB and for the following 24 h was similar in all three groups (P greater than 0.05). It is concluded that pretreatment with carnitine neither facilitates weaning from cardiopulmonary bypass in patients undergoing aortocoronary bypass surgery nor favorably affects hemodynamic function during the next 24 h.

Aged↗