Isoflurane causes vasodilation in the coronary circulation. The current study employed a canine model permitting selective intracoronary administrations of isoflurane (1) to test the hypothesis that coronary vasodilation by isoflurane is mediated by nitric oxide and (2) to evaluate the persistence of coronary vasodilation during an extended exposure to isoflurane.Open-chest dogs anesthetized with fentanyl and midazolam were studied. The left anterior descending coronary artery (LAD) was perfused via extracorporeal system with normal arterial blood or with arterial blood equilibrated with 1.4% (1 MAC) isoflurane. In the LAD bed, coronary blood flow (CBF) was measured with an electromagnetic flowmeter and used to calculate myocardial oxygen consumption (MVO2). In series 1, performed at constant coronary perfusion pressure (CPP), the LAD was exposed to 3 h of isoflurane in two groups of eight dogs: control group, normal coronary endothelium; and experimental group, intracoronary infusion of the nitric oxide synthase inhibitor L-NAME (0.15 mg/min for 30 min). Series 2 was performed with CBF constant; thus, CPP varied directly with coronary vascular resistance. In this series, initial steady-state changes in CPP by isoflurane were evaluated in the same four dogs before and after L-NAME.In the control group of series 1, isoflurane caused a maximal, initial increase in CBF of 444%; however, CBF decreased progressively reaching a value not significantly different from baseline after 3 h of isoflurane. Isoflurane caused a significant (approximately 35%) decrease in MVO2, which persisted during the 3-h administration. Findings after L-NAME (experimental group) were not significantly different from those in control group. In series 2, isoflurane caused significant decreases in CPP that were not affected by L-NAME.The lack of effect of L-NAME on isoflurane-induced coronary vasodilation suggests that nitric oxide does not mediate this response. The increase in CBF during prolonged isoflurane waned over time, perhaps because of tachyphylaxis or emergence of a competitive vasoconstrictor mechanism, e.g., metabolic factors secondary to reduced oxygen demands.
End-Tidal Oxygen Is a Reliable Indicator for Maximal Preoxygenation We thank Drs Benumof and Herway for their comments and acknowledge Dr Benumof’s many contributions to the science and practice of preoxygenation. They are correct in stating that both a poor mask seal and a low-tidal volume ventilation can result in a falsely high end-tidal oxygen (Eto2) value despite poor preoxygenation. However, these situations should not occur if: (1) the Eto2 measurements are interpreted accurately; and (2) the preoxygenation technique is performed correctly. A fundamental principle in interpreting the end-tidal gas measurements is that the tidal volume is sufficient to displace the alveolar dead space. Obviously, if the tidal volume is too small or the patient is apneic, the monitor will display erroneous values. The importance of a sealed system during preoxygenation has been thoroughly addressed in research reports, editorials, and book chapters.1,2 Clinical evidence for a sealed system is an adequate movement of the reservoir bag during inspiration and expiration and a normal capnographic tracing that permits measurement of inspired and end-tidal carbon dioxide (EtCo2).1,2 As stated in our review, “the technique should be performed correctly ...” and “the absence of a normal capnographic tracing and a lower than expected EtCo2 and Eto2 should alert the anesthesiologist to the presence of leaks in the anesthetic circuit.”3 Providing that the Eto2 measurements are accurately interpreted and preoxygenation is properly performed, an Eto2 value ≥90% is a reliable noninvasive indicator of its efficacy. Usha Nimmagadda, MDM. Ramez Salem, MDGeorge J. Crystal, PhDDepartment of AnesthesiologyUniversity of Illinois College of MedicineChicago, Illinois[email protected]
Carbon dioxide (CO2) is an end product of aerobic cellular respiration. In healthy persons, PaCO2 is maintained by physiologic mechanisms within a narrow range (35–45 mm Hg). Both hypercapnia and hypocapnia are encountered in myriad clinical situations. In recent years, the number of hypercapnic patients has increased by the use of smaller tidal volumes to limit lung stretch and injury during mechanical ventilation, so-called permissive hypercapnia. A knowledge and appreciation of the effects of CO2 in the heart are necessary for optimal clinical management in the perioperative and critical care settings. This article reviews, from a historical perspective: (1) the effects of CO2 on coronary blood flow and the mechanisms underlying these effects; (2) the role of endogenously produced CO2 in metabolic control of coronary blood flow and the matching of myocardial oxygen supply to demand; and (3) the direct and reflexogenic actions of CO2 on myocardial contractile function. Clinically relevant issues are addressed, including the role of increased myocardial tissue PCO2 (PmCO2) in the decline in myocardial contractility during coronary hypoperfusion and the increased vulnerability to CO2-induced cardiac depression in patients receiving a β-adrenergic receptor antagonist or with otherwise compromised inotropic reserve. The potential use of real-time measurements of PmO2 to monitor the adequacy of myocardial perfusion in the perioperative period is discussed.
Under certain circumstances, isoflurane is associated with coronary artery vasodilation. The objective of the current study was to ascertain whether the rate of administration of isoflurane influences its vasodilating effect in the coronary circulation.Seven open-chest dogs anesthetized with fentanyl and midazolam were studied. The left anterior descending coronary artery was perfused via either of two pressurized (80 mmHg) reservoirs; reservoir 1 (control) was supplied with arterial blood free of isoflurane, and reservoir 2 was supplied with blood from an extracorporeal oxygenator, which was provided with 95% O2/5% CO2 gas that passed through calibrated vaporizer. Coronary blood flow (CBF) was measured with Doppler flow transducer. In each dog, isoflurane was administered according to two protocols; abrupt (isoflurane-A) or gradual (isoflurane-G). In isoflurane-A, the left anterior descending coronary artery was switched from reservoir 1 to reservoir 2 after the latter was filled with blood previously equilibrated with 1.4% (1 MAC) isoflurane. In isoflurane-G, the left anterior descending coronary artery was switched to reservoir 2 with vaporizer set at 0% isoflurane; then the vaporizer was adjusted to 1.4% isoflurane, which produced a gradual increase in isoflurane concentration within reservoir 2 that reached a level equivalent to that in isoflurane-A (as evaluated by gas chromatography) by 30 min. CBF during maximally dilating, intracoronary infusion of adenosine served as a reference to assess effects of isoflurane.Isoflurane-A caused marked increases in CBF, which, at constant perfusion pressure, reflected pronounced reductions in vascular resistance. These increases in CBF were 80% of those with adenosine. Although isoflurane-G also caused increases in CBF, the increases were only 45% of those caused by isoflurane-A.The current findings demonstrate that the extent of coronary vasodilation by isoflurane was not dependent only on its blood concentration but also on the rate at which this blood concentration was achieved; a gradual increase in blood concentration blunted the vasodilator effect. Differences in the rate of administration of isoflurane likely contributed to its widely variable coronary vasodilating effects in previous studies.
Previous in vivo studies of the coronary vascular effects of halothane (HAL) were complicated by varying hemodynamic conditions and global cardiac work demands.Accordingly, the current study evaluated changes in coronary blood flow (CBF) and associated variables during selective intracoronary administrations of HAL in in situ canine hearts using an extracorporeal-controlled pressure perfusion system. Findings during HAL were compared to those during isoflurane (ISO). The left anterior descending coronary artery (LAD) of 8 open-chest dogs anesthetized with fentanyl and midazolam was perfused at constant pressure (109 +/- 2 mm Hg) with HAL-free arterial blood or with blood equilibrated in an extracorporeal oxygenator with HAL (0.5%, 1.0%, 2.0% in 95% O2-5.0% CO2). In the LAD bed, measurements of CBF were obtained with an electromagnetic flowmeter and used to calculate myocardial oxygen consumption (MVO2). Percent segmental shortening (%SS) was measured with ultrasonic crystals. Changes in CBF by HAL were compared to those during maximal vasodilation with adenosine. Separate studies (n = 5) were performed using 1.4% [1 minimum alveolar anesthetic concentration (MAC)] ISO and the findings compared to those during an equianesthetic (1.0%) concentration of HAL. HAL caused concentration-dependent increases in CBF, and decreases in MVO2 and %SS. With 2.0% HAL, the level of CBF was 50% of the maximal adenosine-induced response. At equianesthetic concentrations, HAL caused increases in CBF that were one-third of those caused by ISO, while the decreases in MVO2 and %SS caused by the drugs were not significantly different. We conclude that HAL has a direct concentration-dependent relaxing action on vascular smooth muscle in the coronary circulation of the in situ canine heart. The ability of HAL to increase CBF significantly while it was reducing local myocardial O2 requirements by a direct negative inotropic effect attests to the potency of this vasodilator action. HAL was a less potent direct coronary vasodilator than ISO, whereas it had a comparable direct negative inotropic effect. (Anesth Analg 1995;80:256-62)
Background Calcium produces constriction in isolated coronary vessels and in the coronary circulation of isolated hearts, but the importance of this mechanism in vivo remains controversial. Methods The left anterior descending coronary arteries of 20 anesthetized dogs whose chests had been opened were perfused at 80 mmHg. Myocardial segmental shortening was measured with ultrasonic crystals and coronary blood flow with a Doppler flow transducer. The coronary arteriovenous oxygen difference was determined and used to calculate myocardial oxygen consumption and the myocardial oxygen extraction ratio. The myocardial oxygen extraction ratio served as an index of effectiveness of metabolic vasodilation. Data were obtained during intracoronary infusions of CaCl2 (5, 10, and 15 mg/min) and compared with those during intracoronary infusions of dobutamine (2.5, 5.0, and 10.0 microg/min). Results CaCl2 caused dose-dependent increases in segmental shortening, accompanied by proportional increases in myocardial oxygen consumption. Although CaCl2 also increased coronary blood flow, these increases were less than proportional to those in myocardial oxygen consumption, and therefore the myocardial oxygen extraction ratio increased. Dobutamine caused dose-dependent increases in segmental shortening and myocardial oxygen consumption that were similar in magnitude to those caused by CaCl2. In contrast to CaCl2, however, the accompanying increases in coronary blood flow were proportional to the increases in myocardial oxygen consumption, with the result that the myocardial oxygen extraction ratio remained constant. Conclusions Calcium has a coronary vasoconstricting effect and a positive inotropic effect in vivo. This vasoconstricting effect impairs coupling of coronary blood flow to the augmented myocardial oxygen demand by metabolic vascular control mechanisms. Dobutamine is an inotropic agent with no apparent direct action on coronary resistance vessels in vivo.
Effects of ionic (Hypaque-76) and nonionic (Isovue-370 and Omnipaque-350) contrast media on oxyhemoglobin dissociation of normal human red blood cells were evaluated. In series 1, 4-mL venous blood samples were obtained from 15 normal human volunteers. One blood sample served as control, and 1 mL of either of the three contrast media was added in vitro to the other 4-mL blood samples. P50 values were estimated from the linear portion of the oxyhemoglobin dissociation curve obtained by tonometry. Determinations of P50 were performed at either pH 7.4 or 7.2. At pH 7.4, P50 in the absence of contrast media was 26.3 ± 0.4 mm Hg (mean ± sem). The contrast media caused comparable decreases in P50 from this value (Hypaque-76, 20.0 ± 0.5 mm Hg; Omnipaque-350, 21.6 ± 0.4 mm Hg; Isovue-370, 20.7 ± 0.4 mm Hg). Reducing pH to 7.2 in the absence of contrast media increased P50 to 33.3 ± 1.0 mm Hg, evidence of the Bohr effect. The presence of contrast media either completely abolished (Hypaque-76 and Omnipaque-350) or markedly attenuated (Isovue-370) this effect. In series 2 (five patients), blood samples were withdrawn from the external iliac artery during injection of Isovue-370 (60–78 mL) into the proximal abdominal aorta to evaluate peripheral vascular disease. Measurement of P50 of these samples yielded findings consistent with those of series 1. The present findings demonstrate that both ionic and nonionic contrast media increase the affinity of hemoglobin for oxygen and, therefore, that they may inhibit oxygen delivery to body tissues.
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