Jan Willem de Jong

Changes in coronary venous inosine concentration and myocardial wall thickening during regional ischemia in the pig.

Correlations between local mechanical and metabolic events were studied during a partial decrease in flow in the left anterior descending coronary artery in 14 open-chest pigs. A decrease in flow to 28% (19–39%) of the control value was achieved with an adjustable screw clamp. A flow probe was placed around the artery. Blood samples were taken from the regional anterior coronary vein and the femoral artery. Myocardial wall thickening was measured with a harpoon type of mercury strain gauge. During ischemia, systolic myocardial wall thickening decreased to 44.5 ± 5.1% (SE) of its control value (P < 0.001). The mean concentrations of plasma potassium and whole blood inosine, hypoxanthine, and lactate in three serial 2-minute samples obtained during a 6-minute control period were compared with those obtained during a 6-minute period of partial occlusion. During ischemia, venous inosine concentration increased from 10.9 ± 0.7 μM to 18.5 ± 1.8 μM (P < 0.005), venous hypoxanthine concentration increased from 28.5 ± 1.4 μM to 33.0 ± 1.5 μM (P < 0.005), venous potassium concentration increased from 3.77 ± 0.10 mM to 4.08 ± 0.13 mM (P < 0.001), and venous lactate concentration increased from 1.04 ± 0.19 mM to 1.52 ± 0.17 mM (P < 0.001). The arterial level of potassium increased very little. The arterial concentration of the other compounds did not change significantly during the 6-minute period of ischemia. Myocardial lactate extraction changed from a control value of 42.6 ± 6.7% to −4.6 = 12.5% (P < 0.05). A negative correlation (rs = −0.79, P < 0.01) was observed between venous inosine concentration and myocardial wall thickening (percent of control) during ischemia. This study indicates that the local venous inosine concentration is a sensitive indicator of regional myocardial ischemia in the pig.

Effects of pacing-induced myocardial ischemia on hypoxanthine efflux from the human heart

Abstract Inosine and hypoxanthine are useful markers of early myocardial ischemia in pigs. In this study the applicability of the products of adenosine triphosphate (ATP) breakdown as markers of myocardial ischemia in man was investigated in 25 patients undergoing diagnostic cardiac catheterization for suspected coronary artery disease. Pacing-induced myocardial ischemia resulted in elevated coronary sinus hypoxanthine levels only after the onset of angina in 18 patients (from 1.2 ± 0.2 μ molar [mean ± standard error of the mean] during the control period to 2.4 ± 0.5 μ molar during ischemia, P

Changes in left ventricular wall dimensions during regional myocardial ischemia

Abstract The relation between changes in left ventricular wall systolic thickening and other measures of left ventricular function were studied during regional ischemia in 14 open chest pigs. A fixed decrease in coronary peak blood flow from 46 ± 5 (standard error) to 13 ± 2 ml/min was produced using a screw clamp and flow probe placed around the left anterior descending coronary artery. Myocardial wall thickness was measured with a calibrated harpoon mercury strain gauge placed through the apical portion of the left ventricle and recorded continuously with left ventricular systolic pressure, the first derivative of left ventricular pressure rise ( dP dt ) and pressure-derived peak velocity of contraction. During systole, the left ventricle thickened by 10.7 ± 2.1 percent of its total average thickness of 12.7 ± 0.7 mm. Within 6 seconds of the onset of ischemia total myocardial wall thickness decreased from 1.356 ± 0.135 to 0.592 ± 0.081 mm ( P

Dose-dependent depression of cardiac function and metabolism by halothane in swine (Sus scrofa).

Halothane depresses myocardial blood flow and metabolism in the dog, but no studies in man have been published. However, the coronary circulation of the pig is remarkably similar to that of man. The authors investigated the effects of halothane-nitrous oxide anesthesia on cardiac function and metabolism in piglets. Thermodilution cardiac output, catheter-tip-manometer measurement of left ventricular function, electromagnetic flowmeter measurement of coronary blood flow, and blood and tissue measurements of gases and metabolites were made during 0.04 (control), 0.46 (low concentration) and 1.04 (high concentration) per cent halothane vaporized in nitrous oxide, 60 per cent: oxygen, 40 per cent. Compared with control, the low concentration decreased cardiac output (CO) by 10 per cent, left ventricular systolic pressure (LVSP) by 30 per cent, peak contractile element velocity (Vmax) by 34 per cent, coronary blood flow (CBF) by 36 per cent, and cardiac oxygen uptake (±o2) by 55 per cent. Compared with control, the high concentration decreased CO by 32 per cent, LVSP and Vmax by 53 per cent, CBF by 63 per cent and ±o2 by 62 per cent. This indicates that the dose-related depression in left ventricular function produced by halothane was accompanied by equivalent decreases in coronary blood flow and oxygen consumption. There was minimal evidence of anaerobic metabolism in these depressed ventricles. Tissue levels of the high-energy phosphates, adenosinetriphosphate and creatine phosphate, and glycogen were unchanged. It is concluded that changes in cardiac oxygenation and metabolism in the pig during halothane anesthesia result from the changes in ventricular function.

Myocardial Functional and Metabolic Responses to Ischemia in Swine during Halothane and Fentanyl Anesthesia

The effect of 60 per cent reduction in flow to the left anterior descending (LAD) coronary artery in young swine during N2O-pan-curonium anesthesia supplemented with either halothane (0.52 per cent end-tidal) or fentanyl (50 μ-kg−1 bolus, 100 μg-kg−1,h−1 infusion) was compared. The presence of ischemia was assessed from coronary arterial-venous (a-v) blood content differences of O2, H+, lactate, K+, and inosine. Cardiac output and left ventricular pressure indices were used to estimate ventricular function. Before stenosis, mean aortic pressure (MAP), left ventricular systolic pressure, (LVSP) rate of rise of LVSP (dP/dt), peak contractile element velocity (Vce Peak), and systemic vascular resistance (SVR) were higher during fentanyl (MAP = 137 mmHg; LVSP = 160 mmHg; LVdP/dt = 2230 mmHgs−1; Vcc Peak = 67 1s−1; SVR = 5,930 dyne·s·cm−5) than during halothane (MAP = 80 mmHg; LVSP = 96 mmHg; LVdP/dt = 930 mmHg·s−1 Vce Peak = 42 1 ·s−1; SVR = 2,945 dyne·s·cm−5). Heart rate (HR), left ventricular end-diastolic pressure (LVEDP), cardiac output (CO) and stroke volume (SV) were not significantly different. LAD coronary blood flow (CBF) and regional myocardial oxygen consumption (Vo2) were also higher during fentanyl (CBF = 40 ml·min−1; Vo2 = 3·5 ml·min−1) than during halothane (CBF = 26 ml·min−1; V02-2·1 ml·min−1). Significant extraction of lactate without v-a differences of K+ and inosine indicated that the hearts during both anesthetics were well-oxygenated. After 30 min of 60 per cent reduction in LADCBF, the metabolic and functional effects were similar during both anesthetics. Lactate extraction changed to production and coronary v-a differences of H+, K+, and inosine became positive or increased. In addition, O2 extraction increased as well. There was little change in HR, SVR, MAP, LVdP/dt, or Vce Peak with either anesthetic, but CO and SV decreased and LVEDP increased during both anesthetics indicating global pump dysfunction. Subsequent to 30 min of reperfusion, the metabolic indices returned towards control although lactate extraction was still lower than before stenosis with both anesthetics. CO and LVdP/dt did not recover with halothane and SV was still depressed with both halo-thane and fentanyl. MAP decreased further with both anesthetics and HR and SVR increased after reperfusion during fentanyl anesthesia. In summary, 60 per cent decrease in LADCBF resulted in equivalent depression in ventricular pump function and degree of ischemia during haltothane or fentanyl supplemented N2O-pancuronium anesthesia in young swine. There was partial recovery both functionally and metabolically with both agents. Thus, the effect of significant stenosis of the LADCA was equvalent whether the hearts has a high (fentanyl) or low (halothane) O2 supply and demand before stenosis.

Purine nucleoside efflux during myocardial ischemia in the pig

SummaryConcentration of whole blood inosine and hypoxanthine was studied in the regional coronary vein in six pigs during a twenty-minute period of myocardial ischemia. The concentration of these purine derivatives was compared to changes in the concentration of whole blood lactate, plasma potassium and to change in myocardial wall systolic thickening (MWT). Partial occlusion of the left anterior coronary artery was produced by placing a screw clamp around the anterior coronary artery. Coronary blood flow was measured using an electromagnetic flow probe. During the ischemic period, flow was decreased on an average to 28.6% of control. MWT was measured by using a harpoon type mercury strain gauge and was observed to decrease to 42.3±14.5% (SE) of control during ischemia (P<.0005). Within two minutes the venous concentration of inosine increased from 9.8±0.6 μM to 20.0±4.3 μM (P<.0025), hypoxanthine increased from 26.0±1.2 μM to 30.6±2.9 μM (P<.10) and lactate increased from 0.79±0.04 mM to 1.17±0.26 mM (P<.025). Venous concentration of potassium and the arterial concentration of the four metabolites did not change significantly. Venous inosine concentration remained significantly elevated during the entire period of ischemia and MWT remained decreased throughout the period. Although lactate and hypoxanthine were elevated, at the two minute period their concentrations gradually decreased during the remainder of the ischemic period. Inosine returned to normal levels upon reinstitution of coronary blood flow and MWT returned to 75.5±10.2% of control. In these studies, venous inosine concentration appeared to be a sensitive measure of myocardial ischemic metabolism.ZusammenfassungDer Vollblutgehat von Inosin und Hypoxanthin wurde bestimmt in lokalvenösen Blutproben von 6 Schweinen während einer Myokard-Ischämie von 20 Minuten. Die Konzentration dieser Purinderivate wurde verglichen mit den Änderungen im Laktat und Kaliumgehalt sowie mit Herzwanddickenänderungen (MWT) Der Ramus anterior descendens der linken Koronararterie wurde mit einer Schraubzwinge verengt, und die Koronardurchblutung wurde mit einem elektromagnetischen Flowmeter gemessen. Während der Ischämieperiode wurde die Durchblutung auf etwa 28,6% des Ausgangswerts gedrosselt. MWT wurde mit einer harpunähnlichen Quecksilberdehnungsmeßbrücke gemessen, sie nahm während der Ischämie um 42,3±14,5% des Ausgangswertes ab (p<0,0005). Innerhalb von 2 Minuten nahm die venöse Konzentration von Inosin von 9,6±0,6 μM auf 20,0±4,3 Mμ zu (p<0,0025). Hypoxanthin nahm von 26,0±1,3 μM auf 30,6 μM±2,9 (p<0,1) zu und Laktat stieg von 0,79±0,04 auf 1,17±0,26 mM (p<0,025). Der venöse Gehalt von Kalium und die arterielle Konzentration der 4 Metabolite änderten sich nicht signifikant. Die venösen Inosinkonzentrationen blieben unverändert hoch während der ganzen Ischämiezeit, und MWT blieb niedrig während dieser Zeit. Obwohl Laktat und Hypoxanthin 2 Minuten nach Ischämiebeginn erhöht waren, nahmen ihre Konzentrationen graduell ab während des weiteren Ischämieverlaufs. Inosin normalisierte sich nach Reperfusion, und MWT erreichte 75% des Ausgangswertes. In der vorliegenden Studie erscheint der venöse Inosingehalt als ein empfindlicher Indikator des Myokardstoffwechsels bei Ischämie.

Is Myocardial Infarct Size Limitation by Ischemic Preconditioning an “All or Nothing” Phenomenon?a

The protective effect of a brief coronary artery occlusion on the development of myocardial necrosis during a subsequent longer lasting occlusion has only a limited duration (“ischemic preconditioning”). 1~ It has not been established, however, how the magnitude of this protective effect changes with time during the reperfusion period following the preconditioning stimulus. Because this knowledge may help elucidating the mechanism underlying ischemic preconditioning, we varied the duration of the reperfusion period following the preconditioning stimulus. Experiments were performed in pigs, a species in which the infirct size-limiting effect of ischemic preconditioning has been demonstrated354 and in which hnctional coronary collaterals are absent so that interpretation ofthe results will not be complicated by a variable residual myocardial blood flow after a coronary artery has been occluded.