Shiro Shimosato

Inotropic effects of isoflurane on mechanics of contraction in isolated cat papillary muscles from normal and failing hearts.

The inotropic effect of isoflurane (Forane) was studied in papillary muscles from cats with normal hearts (NH) and those with experimentally produced congestive heart failure (CHF). Mean maximal velocity of shortening (Vmax) and mean maximal developed force (Fm) of CHF muscles were lower than in the normal heart. Isoflurane at the concentration equivalent to MAC in man reduced Vmax an average of 36 per cent in NH and 51 per cent in CHF muscles. Average percentage decreases in Fm were 40 in NH and 52 in CHF muscles. When changes in myocardial contractility of CHF muscles exposed to isoflurane at MAC were compared with the NH control values, reductions of Vmax and Fm were 75 and 74 per cent, respectively. The combined negative inotropic effects of isoflurane and CHF were more pronounced than that of isoflurane alone on the normal heart.

The Role of the Venous System in Cardiocirculatory Dynamics during Spinal and Epidural Anesthesia in Man

Effects of spinal and epidural anesthesia uncomplicated by premedication or surgery were studied in 20 normal subjects. Venous blood flow, vascular resistance and venous distensibility of forearm and calf vessels were measured simultaneously before and after induction of spinal or epidural anesthesia. In anesthetized calf vessels, blood flow and vascular distensibility increased and vascular resistance decreased. Changes in cardiac output, whether decreased, increased or unchanged, did not affect the ratio of calf blood flow to cardiac output, which in all instances increased following spinal and epidural anesthesia. Changes in arterial blood pressure did not correlate with changes in cardiac output alone or changes in total peripheral resistance alone. However, changes in arterial blood pressure correlated with the interaction of changes in cardiac output and changes in total peripheral resistance. Evidence presented indicates that arterial hypotension induced by either spinal or epidural anesthesia may be due primarily to increased vascular distensibility of capacitance vessels and secondarily to decreased resistivity in pre- and postcapillary resistance vessels in the anesthetized area.

The Effect of Ēthrane on Cardiac Muscle Mechanics

The inotropic effect of Ēthrane on the intrinsic contractile stale of the cat papillary heart muscle was studied in terms of mechanics of contraction. Negative inotropic responses to Ēthrane were compared with those of methoxyflurane and halothane. Ēthrane caused dose-dependent decreases in maximal velocity (Vmax), peak force (Fm), power, and work during isotonic contraction, and was less depressant than halothane and methoxyflurane. A greater concentration of Ēthranc (11 mg/100 ml) was required to produce the same degree of depression (50 per cent) in myocardial power as either methoxyflurane (4 mg/100 ml) or halothane (3 mg/100 ml). Similarly, a 50 per cent reduction in Vmax required a higher concentration of Ēthrane (233 per cent more than halothane and 18 per cent more than methoxyflurane). Therefore, Ēthrane was less depressant to myocardial contractility than methoxyflurane or halothane. Probable mechanisms and significance of the change in the active state resulting from anesthetics are discussed.

Circulatory effects of enflurane in normocarbic human volunteers

SummaryThe circulatory effects of enflurane were studied in ten unmedicated normocarbic volunteers during anaesthesia over a period of 90 minutes or more. Cardiac output did not change significantly during anaesthesia at a mean alveolar anaesthetic concentration of 2.3 volumes per cent and ranging from 1.8 to 3.2. Systolic, diastolic and mean arterial pressures decreased significantly, as did total peripheral resistance. The heart rate increased in all cases. Cardiac output was maintained primarily by an increased heart rate, which compensated for the decreased total peripheral resistance. At recovery, all haemodynamic parameters except heart rate returned to control levels. Minimal change in cardiac output during enflurane anaesthesia in man may be related to the combination of decreased mean arterial pressure and increased heart rate.RésuméLes effets circulatoires de l’enflurane (Ethraneê) ont été étudiés chez dix volontaires normocarbiques non premediques. Le debit cardiaque n’a pas changé de fagon significative durant l’anesthesie é concentration alveolaire de 2.3 vol. pour cent (1.8 a 3.2). Les pressions arterielles systolique, diastolique et moyenne ont diminue k un taux significatif. La fréquence cardiaque augment dans tous les cas, et ceci proportionnellement a la profondeur de l’anesthésie (r = 0.76). La stabilite du debit cardiaque durant l’anesthésie à l’enflurane chez l’homme est due au fait que la baisse de pression arterielle est compensée par 1’augmentation de la frequence cardiaque.

The Effects of Fluroxene and Enflurane on Contractile Performance of Isolated Papillary Muscles from Failing Hearts

Effects of fluroxene and enflurane on myocardial mechanics of isolated papillary muscles obtained from cats with experimental congestive heart failure and from cats with normal hearts were compared. Significant impairment of myocardial performance, with elevated right ventricular pressure and reduced cardiac output, was observed in cats with congestive heart failure. At equipotent anesthetic concentrations (MAC in man) of fluroxene and enflurane, reductions of myocardial performance were similar in the two groups. When changes in maximal velocity of shortening (Vmax) and maximal developed force (Fm) in museles from hearts after congestive heart failure at MAC were compared with control values for normal hearts, depressions were 68 per cent and 70 per cent for fluroxene, and 72 per cent and 68 per cent for enflurane, respectively. These depressions, resulting from the combined effects of congestive heart failure and anesthetic, were similar to those caused by halothane and by isoflurane, but significantly greater than that caused by cyclopropane.

The Effects of Changes in Time Interval of Stimulation on Mechanics of Isolated Heart Muscle and Its Response to Ethrane

The reserve power of myocardial muscle depressed by Ethrane was determined by means of changes in time interval of stimulation in seven isolated cat papillary muscles. Ethrane (average concentration of 6.5 ± 0.1 mg/100 ml) decreaesd maximal isometric forces to 56 per cent of the control value at the “rested-state contraction” (RSC). Ethrane also decreased maximal isometric force (Fm) and rate of force development (dF/dt) at any given time interval of stimulation. Slopes of both time interval-force and time intcrval-dF/dt curves were unaffected by Ethrane. The percentage depressions in Fm and dF/dt were reduced from 44 and 37 to 25 and 21 per cent by decreasing the time interval from 240 sec to 3.2 sec. The ability of heart muscle to respond to changes in time interval of stimulation was, therefore, maintained during administration of Ethrane. Possible mechanisms of myocardial depression induced by Ethrane are discussed.

METHOXAMINE AND CARDIAC OUTPUT IN NONANESTHETIZED MAN AND DURING SPINAL ANESTHESIA.

Methoxamine (approximately 0.2 mg./kg. body weight; range of total dose, 4 to 30 mg.) was given by intravenous infusion to two groups of patients: (1) 5 normotensive, nonanesthetized; and (2) 7 hypotensive under spinal anesthesia. In the nonanesthetized group, the criterion for dosage of methoxamine was elevation and maintenance of arterial blood pressure 25 per cent (±10 per cent) above the resting level. In the hypertensive group, administration of vasopressor was guided by the elevation of arterial blood pressure to the pre-spinal control level. In the normotensive group, cardiac output and the heart rate were both significantly reduced, with variable changes in stroke volume. The vasopressor effect was associated with an elevated total peripheral resistance. In the hypotensive spinal group methoxamine caused variable changes in the cardiac output: increase or decrease in cardiac output depended on changes in stroke volume. The heart rate was generally reduced below the spinal level. The vasopressor effect was apparently due to the elevated total peripheral resistance and, in some instances, to an increased cardiac output. This increase in cardiac output depended mainly on increased stroke volume. These findings suggest that methoxamine in clinical dosage is not a myocardial depressant but a vasopressor capable of increasing the venous return to the heart which responds with increased stroke output.

Hemodynamics of mephentermine in man.

THE clinical use of mephentermine¶ to elevate the arterial-blood pressure in man is presumably based upon the rationale that its pressor action is primarily due to an increase in myocardial contrac...

Effect of Halothane on Force-Velocity Relations and Dynamic Stiffness of Isolated Heart Muscle

The effect of halothane on isometric and isotonic contraction of isolated cat papillary muscle was studied employing the Hill model of muscular contraction. Maximal velocity of shortening and maximal force both were depressed by increasing halothane concentrations, resulting in successive downward shifts of force-velocity curves. Net shortening, power and work of isotonic contraction also exhibited a dose-dependent depression. Dynamic stiffness of the series elastic element of the myocardium was unaltered by halothane. The findings indicate that the negative inotropism induced by halothane is the result of a dose-dependent depression of the intensity of energy conversion by the contractile element of heart muscle.

The effect of methoxyflurane on the inotropic state of myocardial muscle.

The direct effect of methoxyflurane upon the inotropic state of the myocardium was studied in an isolated cat papillary heart muscle preparation. Methoxyflurane decreased muscle ability to develop force and shorten and the velocity of shortening for a given load (power). The decrease in the inotropic state of muscle was dose-dependent, as evidenced by progressive decreases in maximum velocity of myocardial muscle shortening (Vmax) power, and work. Methoxyflurane also caused changes in the active state of the myocardium (force-generating processes), as shown by decreases in maximum rate of force development (dF/dt) and time-to-peak isometric force (TTFm). The results suggest that methoxyflurane exerts a negative inotropic effect on the intrinsic contractile state of cardiac muscle owing to alteration in the mechanical energy derived from chemical reactions within the contractile system.