Reversal of volatile anesthetic-induced depression of myocardial contractility by extracellular calcium also enhances left ventricular diastolic function.
BACKGROUND
Volatile anesthetics depress global left ventricular function by altering intracellular calcium (Ca2+) homeostasis at several sites within the myocyte. Although extracellular Ca2+ partially reverses the negative inotropic effects of volatile anesthetics, the actions of extracellular Ca2+ on anesthetic-induced diastolic dysfunction are unexplored. This investigation examined and compared the direct effects of extracellular Ca2+ on left ventricular systolic and diastolic function in conscious and anesthetized dogs.


METHODS
Experiments were conducted in the presence of pharmacologic blockade of the autonomic nervous system because autonomic nervous activity may significantly influence the hemodynamic actions of anesthetics and Ca2+ in vivo. Three groups comprised a total of 27 experiments conducted using nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dt, subendocardial segment length, and cardiac output. Myocardial contractility was evaluated using the preload recruitable stroke work relationship slope (Mw). Diastolic function was assessed using a time constant of isovolumic relaxation (tau), a regional chamber stiffness constant (Kp), and maximum segment lengthening velocity during rapid ventricular filling (dL/dtE) and atrial systole (dL/dtA). On 3 separate days, a CaCl2 infusion at 1.25, 2.5, or 5 mg.kg-1 x min-1 was administered. Hemodynamics and ventricular pressure-length loops were recorded after a 20-min equilibration at each dose in the conscious state or during halothane or isoflurane anesthesia.


RESULTS
In conscious dogs, CaCl2 produced a significant (P < .05) and dose-dependent increase in contractility as evaluated by Mw. In the presence of halothane anesthesia, CaCl2 increased contractility (Mw of 26 +/- 5 mmHg to 78 +/- 10 mmHg during the high dose of CaCl2), enhanced isovolumic relaxation (tau of 57.9 +/- 4.2 ms to 41.1 +/- 1.9 ms during the high dose of CaCl2), improved rapid ventricular filling (dL/dtE of 11.8 +/- 1.4 mm/s to 20.2 +/- 1.6 mm/s during the high dose of CaCl2), and reduced regional chamber stiffness (Kp of 0.70 +/- 0.18 mm-1 to 0.38 +/- 0.04 mm-1 during the high dose of CaCl2). Similar findings were observed when CaCl2 was administered to dogs anesthetized with isoflurane.


CONCLUSIONS
Although CaCl2 produced positive inotropic effects in both the conscious and anesthetized states, CaCl2 did not alter diastolic function in conscious dogs. In contrast, CaCl2 reversed halothane- and isoflurane-induced negative lusitropic actions. The results of the present investigation suggest that improvement of left ventricular performance by CaCl2 during volatile anesthesia may be related to actions in diastole as well as systole.
Pagel
P S
PS
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Kampine
J P
JP
Schmeling
W T
WT
Warltier
D C
DC
D000769:Anesthesia, Inhalation; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D003864:Depression, Chemical; D003971:Diastole / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D006221:Halothane / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007530:Isoflurane / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D002316:Cardiotonic Agents; D007530:Isoflurane; D002122:Calcium Chloride; D006221:Halothane