Walton-Brodie Strain Gauge Arch Research Articles

Relative significance of dopamine receptors, beta adrenoceptors and norepinephrine uptake inhibition in the cardiovascular actions of dopexamine hydrochloride

Studies in our laboratory have confirmed that dopexamine hydrochloride is a potent beta 2-adrenoceptor and DA1-dopamine receptor agonist. We examined the effects of dopexamine hydrochloride on both cardiac contractile force, determined by use of a Walton-Brodie strain-gauge arch sutured to the right ventricle, and heart rate in anesthetized dogs. Dopexamine hydrochloride increased cardiac contractile force and heart rate and decreased blood pressure. After administration of the ganglionic blocking agents, hexamethonium and atropine, or the selective beta 1-adrenoceptor antagonist, atenolol, the positive inotropic and chronotropic effects of dopexamine hydrochloride were reduced or eliminated, demonstrating that the drug had little or no direct beta 1-adrenoceptor action and that a myocardial beta 2-adrenoceptor action was not involved in its cardiac effects. During these investigations, dopexamine hydrochloride was found to be an inhibitor of norepinephrine uptake, potentiating the cardiac effects of both exogenously administered norepinephrine and norepinephrine released from sympathetic nerves. These results led to the following conclusions: Dopexamine hydrochloride stimulates the heart by 2 mechanisms--(1) baroreceptor-mediated release of norepinephrine resulting from hypotension produced by beta 2 adrenoceptor and DA1 dopamine receptor-mediated vasodilatation, and (2) potentiation of the released norepinephrine due to prevention of norepinephrine uptake by sympathetic nerves. The latter mechanism may be involved in the cardiac stimulation observed in patients with congestive heart failure and shock, since excessive sympathetic activity and elevated catecholamine levels are present in these conditions.

Use of the Walton-Brodie Strain Gauge Arch to Measure Contractile Force During Anaesthesia

The Walton-Brodie strain gauge arch is an instrument that quantitatively measures CF. Like many methods, the strain gauge arch is affected by loading conditions and heart rate. Nevertheless, this methodology, when properly used, has proved very useful in describing the direct action of anaesthetic drugs. Knowledge from strain gauge arch use has stimulated research to explain the negative inotropic effect of anaesthetics and helped clinicians understand the cardiovascular effects of drugs that they may wish to use.

Protective effect of chronic versus acute cardiac denervation on contractile force during coronary occlusion

The effects of acute coronary artery (CA) occlusion on myocardial contractile force were studied in mongrel dogs with (1) chronically denervated hearts (n = 10), (2) acutely denervated hearts (n = 5), and (3) normally innervated hearts (n = 6). Contractile force was measured in ischemic and nonischemic areas using Walton-Brodie strain gauge arches sutured to the epicardium. Coronary occlusion was accomplished by ligating several small branches of the left anterior descending and the circumflex arteries supplying the apical region on the left ventricle. Following occlusion, contractile force in the ischemic area decreased by 66.8% in the control group, by 73.6% in the acutely denervated group, but only by 21.6% (P less than 0.001) in the chronically denervated group. These results demonstrate that chronic cardiac denervation protects from the severe loss of contractile force in the ischemic area. This salutary effect is not seen with acute cardiac denervation.

Release of autonomic neuromediators by local ventricular electrical stimulation.

Trains of electrical stimuli were applied to the ventricular epicardium in pentobarbital-anesthetized dogs. The trains, delivered during the absolute refractory period via Walton-Brodie strain gauge arches, resulted in a highly localized potentiation of ventricular contractile force. The magnitude of the potentiation was directly related to the intensity of the trains. The positive inotropic response of either ventricle to trains of stimuli was abolished following chronic cardiac denervation or beta-adrenergic blockade with tolamolol, indicating that the response was probably mediated by the excitation of local sympathetic nerve fibers. Following the elimination of adrenergic influences, a slight negative inotropic response to trains of stimuli was observed in some animals. Administration of atropine blocked the negative inotropic response. When the adrenergic system was intact the administration of atropine resulted in a significant augmentation of the positive inotropic response of both ventricles to trains of stimuli. Thus in addition to norepinephrine release, it also appeared that electrical stimulation of the ventricles resulted in activation of local parasympathetic fibers with subsequent release of acetylcholine.

Miniature force transducer for myocardial stimulation and local tension measurements.

The commercially available transducers for direct measurement of myocardial tension are either large in size or lack the ability of isometric measurement. Moreover, none of them enables measurement of local isometric tension just around the site of electrical stimulation of the heart. A miniature strain gauge transducer was developed in our laboratories and is herewith described. It weighs 150 mg, and consists of two arms with adjustable distance between 1-5 mm. It is applied to the heart by 2 needles which may serve also as stimulating or sensing electrodes. A full bridge made of constantan foil strain gauges ensures low drift. The device enables in vivo measurement of isometric tension of a myocardial segment of the site where the tension is being measured and permits simultaneous recording of the electrogram. Attachment of the gauge to the ventricular wall by means of needles makes simple the transfer of the transducer from one measuring point to another. The performance of the miniature force transducer was compared to that of a standard Walton-Brodie strain gauge arch demonstrating marked similarity of response at low heart rates. At high frequencies however differences in mechanical response of the heart were obtained by the two force transducers.

Effects of Fluorocarbons, Chlorinated Solvents, and Inosine on the Cardiopulmonary System

The effects of fluorocarbons and chlorinated solvents on the cardiopulmonary system are reviewed. The new information, not hitherto reported, relates to the antagonistic action of inosine, a naturally occurring nucleoside formed in the body by deamination of adenosine. The effect of inosine on methylene chloride toxicity was investigated in open chest dogs anesthetized with pentobarbital sodium. Methylene chloride (5% in air or 50,000 ppm) elicited a decrease of ventricular contractility represented by the diminished left ventricular (dp/dt)max and myocardial contractile force measured directly with a Walton-Brodie strain gauge arch. Coronary blood flow decreased slightly after exposure to methylene chloride. Arterial blood pressure and heart rate did not change. The negative inotropic effect of methylene chloride was reversed or prevented to a substantial extent by intravenous infusion of inosine (5 mg/kg-min). The effect of the latter compound was also characterized by significant coronary vasodilation. It was shown by the experiments that the cardiostimulatory action of inosine was associated with improved hypoxic adaptability of the coronary blood vessels. In contrast, the effect of catecholamines (epinephrine and isoproterenol) was not accompanied by such a beneficial coronary vascular effect. On the basis of these results, the conclusion has been arrived at that inosine might be recommended as a useful antidote in methylene chloride poisoning in particular, and of poisoning by chlorinated solvents and fluorocarbons in general.

Effects of fluorocarbons, chlorinated solvents, and inosine on the cardiopulmonary system.

The effects of fluorocarbons and chlorinated solvents on the cardiopulmonary system are reviewed. The new information, not hitherto reported, relates to the antagonistic action of inosine, a naturally occurring nucleoside formed in the body by deamination of adenosine. The effect of inosine on methylene chloride toxicity was investigated in open chest dogs anesthetized with pentobarbital sodium. Methylene chloride (5% in air or 50,000 ppm) elicited a decrease of ventricular contractility represented by the diminished left ventricular (dp/dt)(max) and myocardial contractile force measured directly with a Walton-Brodie strain gauge arch. Coronary blood flow decreased slightly after exposure to methylene chloride. Arterial blood pressure and heart rate did not change. The negative inotropic effect of methylene chloride was reversed or prevented to a substantial extent by intravenous infusion of inosine (5 mg/kg-min). The effect of the latter compound was also characterized by significant coronary vasodilation. It was shown by the experiments that the cardiostimulatory action of inosine was associated with improved hypoxic adaptability of the coronary blood vessels. In contrast, the effect of catecholamines (epinephrine and isoproterenol) was not accompanied by such a beneficial coronary vascular effect. On the basis of these results, the conclusion has been arrived at that inosine might be recommended as a useful antidote in methylene chloride poisoning in particular, and of poisoning by chlorinated solvents and fluorocarbons in general.

Responses of the canine myocardium to stimulation of thoracic cardiac nerves.

The thoracic cardiac nerves were stimulated in each of 21 dogs anesthetized with alpha chloralose. Recordings were made of heart rate, blood pressure, and contractile force from all four cardiac chambers. Walton-Brodie strain-gauge arches were sutured to both atria, and to three locations of each ventricle, representing both anterior and posterior surfaces. The functional autonomic components of each nerve were summarized and classified into four basic types. Types I and II were both located medial to the thoracic vagi. These were shown to contain both sympathetic and parasympathetic components traveling to all four chambers of the heart. The sympathetic componnent of the type II nerves produced reflex changes in force of contraction and systemic blood pressure. Nerves classified as types III and IV produced no parasympathetic effect on the heart. These were all located lateral to the thoracic vagi. While the type III nerves carried sympathetic efferent fibers to all four chambers, the type IV nerve carried sympathetic fibers predominantly to the right atrium.

A depressed response of left ventricular contractile force to isoproterenol and norepinephrine in dogs with congestive heart failure

The inotropic response of the left ventricle to intravenous administration of norepinephrine (NE) and isoproterenol (I) was studied in dogs with congestive heart failure (CHF) resulting from aortocaval fistula. Left ventricular contractile force (CF) was recorded at the peak of the length-tension curve with a modified Walton-Brodie strain gauge arch in five dogs with CHF and five control animals. Arterial blood pressure (ABP) and heart rate (HR) were also monitored. Graded dose-response curves (0.0125 to 1.6 mug per kilogram) were obtained to NE and I. The response of CF was significantly depressed at all dose levels to both NE and I ni dogs with CHF. For example, at the dose of 0.8 mug per kilogram the CF response to I in the control dogs was 201 +/- 32 per cent above control level, whereas in CHF dogs the response was 92 +/- 31.5 per cent. Similarly, NE at this dose level produced a 168.6 +/- 14.7 per cent increase in CF in control dogs and 71 +/- 21.3 per cent in CHF dogs. I was approximately four times as potent as NE and this ratio was not altered in CHF dogs. The response of HR and diastolic ABP to drug administration was not altered by CHF. These data clearly suggest a depressed inotropic response to beta-adrenergic stimulation in this CHF model and a separation of the inotropic and chronotropic response.

Propranolol in experimental myocardial ischemia: Dissociation of effects on contraction and epicardial ST segments

Recent studies have suggested that propranolol decreases the extent of myocardial injury in acute ischemia. Although other studies have shown that global myocardial performance is depressed, zonal effects of propranolol in this setting are unknown. Therefore, the effect of propranolol (1.0 mg. per kilogram) was investigated in nine dogs with the use of Walton-Brodie strain gauge arches and local epicardial electrograms (10 to 12 sites). The heart rate effects of propranolol were controlled by atrial pacing. After coronary occlusion, heart rate increased slightly without a significant change in blood pressure. Following the infusion of propranolol, heart rate decreased significantly from 165.0 +/- 3.5 to 126.2 +/- 4.7 beats per minute (p less than 0.001) while both the systolic and diastolic blood pressures showed insignificant changes. After coronary occlusion, nonischemic zone tension showed no significant changes; however, propranolol decreased total tension from 105.2 +/- 2.5 per cent to 66.8 +/- 4.7 (p less than 0.001). Similarly, propranolol further decreased total tension in the border zone from 84.4 +/- 6.7 per cent (p less than .02) to 50.6 +/- 5.1 (p less than 0.01). Ischemic zone tension also fell further (p less than 0.025) after propranolol. Restoration of prepropranolol heart rate had no significant effect on tension development. Following coronary occlusion, sigmaST increased from 5.7 +/- 2.2 to 72.9 +/- 20.1 mv. (p less than 0.001). Coincident with the decrease in heart rate and tension development induced by propranolol, sigmaST decreased to 60.8 +/- 18.8 mv. (p less than 0.05). When the heart rate was restored to prepropranolol level, sigmaST again rose to 73.2 +/- 16.9 mv. (p less than .005). Thus, propranolol does effect an improvement in ischemic injury which is related, at least in part, to the induced decrease in heart rate. A concomitant substantial decrease in local tension development also occurs, however. The latter observations may limit the potential usefulness of propranolol in this setting.

Effect of nitroprusside on local contractile performance after coronary ligation and reperfusion

To study the effects of nitroprusside infusion on the regional contractile performance of the left ventricle after coronary occlusion, local tension and segment length of the ischemic, border and nonischemic zones were studied using Walton-Brodie strain gauge arches and mercury-in-Silastic tubing segment length gauges in open chest dogs. The effect of this intervention on the time period for functional reversibility of the affected areas after revascularization was also examined. Fifteen minutes after occlusion of the left anterior descending coronary artery, nitroprusside (4 to 11 μg/kg per min) was infused to keep systolic pressure 20 to 25 percent below control levels for 2 hours after occlusion and then 1 hour after reperfusion. The ischemic zone showed no change in either tension or length although there was a gradual continuing decrease in tension. However, in the border zone, total tension, which had decreased to 81.4 ± 9.6 (standard error of the mean) percent of control level 15 minutes after coronary occlusion, increased to 87.5 ± 11.3 percent immediately after nitroprusside infusion and continued at that level for 2 hours. Preejection tension, rate of tension rise and ejection tension demonstrated parallel increases. Segment length, which had increased to 144.1 ± 4.5 percent of control level after coronary occlusion, declined to 115 ± 10.7 percent ( P < 0.02) immediately after the onset of infusion. The nonischemic zone showed a sustained increase in all tension variables ( P < 0.01) and a decrease in segment length during the period of nitroprusside infusion with a return to control value after discontinuation of the infusion. The immediate deterioration in tension in the ischemic zone caused by reperfusion after 2 hours of occlusion was prevented by nitroprusside. The border zone continued to maintain improved tension after reperfusion but exhibited an immediate decrease from 84.1 ± 7.8 percent to 69.1 ± 11.7 percent ( P < 0.05) after discontinuation of nitroprusside. In summary, nitroprusside infusion provides a sustained increase in tension and decrease in length of the border and the nonischemic zones after acute coronary occlusion whereas the ischemic zone remains unaffected. Although administration of nitroprusside fails to prolong the time period for functional reversibility of the affected zones with reperfusion, it appears to prevent further deterioration.

Temporal relation of epicardial electrographic, contractile and biochemical changes after acute coronary occlusion and reperfusion

The increasing use of changes in the S-T segment of local epicardial electrograms to quantitate myocardial infarct size has led to the need for a better understanding of this method. Accordingly, we studied the local electrographic, tension and biochemical changes that occurred after coronary occlusion and subsequent reperfusion in 44 dogs using epicardial electrograms from 10 to 12 sites, Walton-Brodie strain gauge arches and myocardial ratios of potassium ion to sodium ion ( K + Na + ). After coronary occlusion for 1 hour, total S-T segment elevation increased from 10.2 ± 2.4 to 78.3 ± 13.7 mv ( P < 0.001) and tension development decreased to 63.6 ± 7.0 percent of control value ( P < 0.001); occlusion for 3 hours resulted in a total S-T segment elevation increase from 5.8 ± 3.4 to 56.7 ± 8.7 mv ( P < 0.001) and a tension decrease to 61.4 ± 5.3 percent ( P < 0.001) of control value. After reperfusion two types of response were observed. In nine experiments new local pathologic Q waves appeared in an average of 5.3 of 8.2 ischemic electrode sites within 5 to 10 minutes of reperfusion concomitant with a marked further decrease in total tension from 67.3 ± 05.5 percent to 42.4 ± 6.0 percent of control value ( P < 0.001). Simultaneously, total S-T elevation decreased from 66.1 ± 8.2 to 25.3 ± 3.4 mv ( P < 0.001). In seven experiments no Q waves appeared after reperfusion and there was no significant change in tension. Total S-T elevation again decreased from 58.3 ± 12.7 to 27.1 ± 5.7 mv ( P < 0.025). When normal saline solution was perfused distal to the coronary arterial occlusion total S-T elevation decreased from 68.0 ± 3.6 to 36.3 ± 5.2 mv ( P < 0.001). After 3 hours of coronary occlusion, myocardial K + decreased and Na + increased in the ischemic zone, resulting in a significant decrease in the K + Na + ratio ( P < 0.005). Reperfusion for 2 hours resulted in a further depletion of K + and an increase in Na + with a resultant complete reversal of the K + Na + ratio ( P < 0.001). In summary, after reperfusion the S-T segment abnormalities rapidly decreased in all experiments despite the appearance of new Q waves in more than half of these studies concomitant with either a decrease or no change in contractile ability and continuing myocardial K + loss and Na + accumulation. S-T segment mapping therefore appears to be of limited value in assessing the effect of reperfusion on infarct size. The decrease in S-T segments that occurred with perfusion of either blood or saline solution suggests a “washout” phenomenon.

Nitroglycerin in experimental myocardial infarction effects on regional left ventricular length and tension

Controversy has existed concerning the value of nitroglycerin therapy in acute myocardial infarction. With use of Walton-Brodie strain gauge arches and mercury-in-Silastic segment length gauges, the effects of nitroglycerin (30 μg/kg intravenously) were studied on local tension and length characteristics of the ischemic, border and nonischemic zones of the left ventricle in 10 open chest dogs. In the nonischemic zone total tension increased to 144.8 ± 13.6 (mean ± standard error of the mean) percent ( P <0.005) of control levels, and segment length decreased to 79.4 ± 4.4 percent ( P <0.01) with infusion of nitroglycerin 15 to 30 minutes after coronary ligation. Changes were similar in the groups given nitroglycerin 45 to 60 minutes and 2 to 3 hours after ligation. The border zone exhibited an increase in total tension to 132.3 ± 8.4 percent ( P <0.005) of control level and a decrease in segment length to 79.0 ± 2.4 percent ( P <0.001) in the 15 to 30 minute group. In the 45 to 60 minute group, tension increased to 117.9 ± 4.8 percent ( P <0.005), whereas length decreased to 86.8 ± 1.4 percent ( P <0.001); and in the 2 to 3 hour group tension increased to 124.9 ± 6.0 percent ( P <0.005), and length decreased to 91.9 ± 3.5 percent ( P <0.001). The decrease in magnitude of responsiveness in the 45 to 60 minute and 2 to 3 hour postligation groups compared with the 15 to 30 minute postligation group was highly significant ( P <0.005). The central ischemic zone showed no significant change in tension or length in any group. Maximal response to nitroglycerin administration in both tension and length parameters was observed within 30 to 60 seconds and was concomitant with a decrease in systolic pressure to 73.3 ± 1.9 percent ( P <0.001) and an increase in heart rate to 107.2 ± 1.0 percent. Nitroglycerin improves the contractile performance of the nonischemic and border zones after coronary occlusion without affecting the central ischemic zone. However, the border zone exhibits a progressive decrease in contractile response as a function of time. These data suggest that nitroglycerin has the overall effect of functionally reducing the extent of the ischemic area and strongly supports its potential clinical usefulness in acute myocardial infarction.

Digitalis in experimental acute myocardial infarction: Differential effects on contractile performance of ischemic, border and nonischemic ventricular zones in the dog

The effects of digoxin (priming dose of 0.04 mg/kg body weight followed by infusion of 0.02 mg/kg per min) on local tension and length characteristics of the nonischemic, border and ischemic left ventricular zones were studied in 30 dogs using Walton-Brodie strain gauge arches and mercury-in-Silastic segment length gauges. Total tension in the nonischemic zone increased to 130.9 ± 5.3 percent ( P < 0.001) of the control level in association with parallel changes in preejection and ejection tension and rate of rise of tension when infusion of digoxin was instituted 15 to 30 minutes after ligation. Consistent increases in tension variables were noticed when infusion of digitalis was initiated 45 to 60 minutes or 2 to 3 hours after ligation. Segment length remained unchanged. In the border zone, total tension decreased to 68.9 ± 5.9 percent ( P < 0.01) 15 to 30 minutes after coronary occlusion and increased to 106.8 ± 9.7 percent ( P < 0.01) after infusion of digitalis. When infusion of digitalis was instituted 45 to 60 minutes or 2 to 3 hours after occlusion, similar increases in total tension and other tension variables were seen. Segment length again showed no significant changes. There was an increase in total tension in 5 of the 12 ischemic zones studied when digitalis was infused 15 to 30 minutes after coronary arterial ligation, whereas a consistent (3 to 5 percent) decrease in tension was observed when infusion of digitalis was instituted 45 to 60 minutes and 2 to 3 hours after coronary occlusion. There was no increase in segment length. In summary, digitalis uniformly increased contraction of the nonischemic and border zones after coronary arterial ligation, but the effects on contraction and aneurysmal bulging in the ischemic zone were minimal.

Papillary muscle dynamics: in situ function and responses of the papillary muscle.

Experiments were designed to 1) study in situ changes in papillary muscle length and force during the cardiac cycle, 2) investigate the relationship between papillary muscle length and maximal ventricular pressure, 3) study the effect of both positive and negative inotropic intervention on this relationship. A mercury gauge transduceror Walton-Brodie strain-gauge arch was sutured to the anterior papillary muscleand used to measure the extent of shortening or lengthening (deltaL) or force (APMF),.respectively. The anterior papillary muscle showed rapid increase of length and forcewhile contracting during isovolumic contraction and reached peak systolic length at end-isovolumic contraction or during the early injection phase. The papillary muscle was observed to shorten during the phases of ejection and isovolumic relaxation. It was concluded that changes in ventricular pressure during the cardiac cycle are associated with changes in papillary muscle length and force such that the resulting "lengthening contraction force" is appropiate for maintenance of normal atrioventricular valve function during isovolumic contraction. There was an inverse relationship between deltaL and maximal ventricular pressure such that for each increment in peak ventricular pressure there was a decrease in deltaL. The deltaL-force relationship was shifted upward and to the right by norepinephrine (NE) and isoproterenol and downward and to the left by occlusion of the posterior vena cava. Phenylephrine had little or no effect on this relationship.

Contractile and electrophysiological responses to progressive digitalis toxicity.

Contractile force and intraventricular conduction during progressive ouabain infusion were examined in 15 dogs using a Walton-Brodie strain gauge arch and sequential atrial and bundle of His pacing. This permitted: (1) contractile force determination; (2) overdrive of arrhythmias; (3) maintenance of normal contraction sequences; (4) 'normal' ventricular depolarization; (5) rate control; (6) conduction measurements of the H-V interval (His-Purkinje conduction), QRS (intramyocardial conduction), and H-S interval (total intraventricular conduction). Contractile force increased 21.2 plus or minus 4.3% at the onset of toxicity. After toxicity, there was a significant further increase (P smaller than 0.01) to 50.1 plus or minus 12.4%. However, immediately before ventricular fibrillation, a 43.8 plus or minus 8.2% decrease occurred (P smaller than 0.01). H-V time showed no change (from 30 plus or minus 2.7 to 31.5 plus or minus 2.4 ms) at the onset of toxicity but after toxicity, it lengthened to 40.5 plus or minus 3.1 ms (P smaller than 0.05). QRS did show significant prolongation (69.5% plus or minus 5.3 to 79.5 plus or minus 6.9 ms; P smaller than 0.05) at the onset of toxicity, but this was more marked (79.5 plus or minus 6.9 to 130.5 plus or minus 8.1 ms; Pplus or minus 0.01) after toxicity. H-S time was significantly prolonged (99.5 plus or minus 6.2 to 111.0 plus or minus 8.9 ms) before (P smaller than 0.02) and after (P smaller than 0.01) toxicity (111.0 plus or minus 8.9 to 171.1 plus or minus 10.6 ms). During toxicity there is progressive increase in contractile force with continued ouabain infusion Progressive prolongation of intramyocardial conduction occurs in nontoxic and toxic doses, but His-Purkinje conduction is prolonged only in supratoxic doses.

Maximal rate of the left ventricular pressure fall (peak negative dP/dt) in early stage of myocardial ischemia following experimental coronary occlusion.

Short-term, repeated myocardial ischemia was produced in 20 opened-chest anesthetized dogs by left anterior descending (LAD) branch occlusion. Left ventricular pressure (LVP) and its dP/dt were recorded by Satham SF-1 transducer, and isometric local force (F) was measured by a Walton-Brodie strain gauge arch sewn onto LV free wall. In all experiments, within a few beats after LAD occlusion, peak negative dP/dt started to diminish its amplitude, reaching a nadir after 20-30 sec (63 +/- 5% of control, 9 dogs). It recovered to 83 +/- 3% of control level in 45 sec and remained essentially unchanged thereafter. This change preceded those of LVP and max dP/dt, which showed only minor falls. In 6 dogs, changes by occluding root of LAD were compared with those by its branch occlusion. The greater the extent of ischemia, the more marked and prolonged were the changes. While F in the ischemic center (Fc) rapidly lost its contractile activity following LAD occlusion, F in marginal zone between infarcted and non-infarcted region (Fm) showed variable extent and different time-course of its diminution. Thus, it was concluded that the change in peak negative dP/dt following LAD occlusion was one of the sensitive signs of early ischemic changes, and was attributed at least in part to characteristic changes in contractile activity of myocardium surrounding the ischemic injury.

Effects of altered ventricular load on the Walton-Brodie strain gauge arch.

Effects of altered ventricular load on the Walton-Brodie strain gauge arch.

Cardiovascular effects of a newer antiarrhythmic agent, disopyramide phosphate

The effect on myocardial contractility of a new antiarrhythmic drug, disopyramide phosphate, was investigated and compared with that of quinidine using a Walton-Brodie strain gauge arch. Quinidine and disopyramide phosphate were compared at the same dosage, ranging from 1 to 10 mg. per kilogram of body weight. At 1 mg. per kilogram of body weight, the contractile force was unaffected by quinidine but was depressed 42 per cent by disopyramide phosphate. At higher dose (5 to 10 mg. per kilogram of body weight) the contractile force was depressed 50 to 100 per cent more by disopyramide phosphate than by quinidine. End-diastolic muscle segment length increased 5 per cent with disopyramide phosphate at 1 mg. per kilogram of body weight, whereas no change was observed with quinidine at this dosage. Both drugs widened QRS and P duration and prolonged PR interval to the same degree. Disopyramide appears to have no beta-adrenergic blocking activity, since it did not alter the contractile force or arterial blood pressure responses to isoproterenol, norepinephrine, or tyramine. Coronary blood flow was decreased by both drugs. The cardiac depressant effect of disopyramide phosphate would appear to limit its usefulness, but for the same degree of cardiac depression, disopyramide phosphate exhibited fewer ECG abnormalities and hence could be used as a replacement therapy for quinidine.

Importance of the carotid sinus baroreceptors in the regulation of myocardial performance.

The question of whether the carotid sinus baroreceptors modulate myocardial performance remains controversial. Several studies that have stressed their importance have been criticized because the possible role of cerebral ischemia and of other important variables was not eliminated. To reinvestigate this problem, we studied 21 dogs placed on total cardiopulmonary bypass. In each of these animals the carotid sinus regions were isolated and perfused with fully oxygenated blood at a constant flow rate; perfusion pressure was changed by varying the resistance to outflow from the isolated segments. Several indices of myocardial performance were assessed: right and left ventricular contractile force with Walton-Brodie strain gauge arches; the maximal rate of change in contractile force, dF/dt; the pressure developed within an isovolumic balloon inserted into the left ventricle; and the maximal rate of change of this pressure, dP/dt. When the pressure distending the carotid sinuses was raised from an average value of 34.1 +/-2.8 (SEM) mm Hg to 190.1 +/-4.7 mm Hg, right ventricular contractile force fell 14.9 +/-2.3% (P < 0.001); right ventricular dF/dt decreased 16.7 +/-3.0% (P < 0.01); left ventricular contractile force declined 14.9 +/-3.3% (P < 0.01); left ventricular dF/dt fell 19.3 +/-4.0% (P < 0.01); peak systolic pressure in the isovolumic balloon declined 18.2 +/-3.7% (P < 0.001); and dP/dt decreased 34.1 +/-4.0% (P < 0.01). Prior adrenalectomy and vagotomy and maintenance of heart rate at a constant level did not influence these results. The inverse relation between carotid sinus perfusion pressure and the indices of contractility that was observed in this investigation strongly suggests that the carotid sinus baroreceptors are an important regulatory mechanism in the control of myocardial performance.