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R J Applegate

Publications and source records attributed to R J Applegate.

38 records · Page 3Linked to original sources
PubMed1987

Frequency-dependent myocardial depression induced by verapamil in conscious dogs.

To determine the effects of calcium entry-blocking drugs on the frequency-dependent rate of peak positive left ventricular pressure development [(+)dP/dtmax] we evaluated the effects of incremental left atrial pacing during verapamil, diltiazem, and nifedipine under equivalent loading conditions in seven conscious preinstrumented mongrel dogs. To eliminate the effects of reflex sympathetic stimulation the animals were pretreated with propranolol (2 mg/kg). Prior to atrial pacing (+)dP/dtmax was similar for verapamil [2,392 +/- 416 (SD) mmHg/s], diltiazem (2,661 +/- 606 mmHg/s), and nifedipine (2,731 +/- 636 mmHg/s), P = NS among drugs. At a common peak paced heart rate (150 beats/min) under equivalent loading conditions, (+)dP/dtmax was significantly reduced from the corresponding preatrial pacing value only after verapamil (2,131 +/- 415 mmHg/s, P less than 0.03) and was significantly lower than after either diltiazem (2,547 +/- 550 mmHg/s) or nifedipine (2,633 +/- 705 mmHg/s, P less than 0.04). No significant linear relation was observed between stimulation frequency and (+)dP/dtmax during atrial pacing alone (slope = -2.2 +/- 1.3, r = -0.30 +/- 0.23, P = 0.12), during atrial pacing with beta-blockade alone (slope = 1.7 +/- 1.5, r = 0.24 +/- 0.25, P = 0.25), or beta-blockade combined with diltiazem (slope = -0.91 +/- 1.3, r = 0.02 +/- 0.23, P = 0.38) or nifedipine (slope = -1.2 +/- 1.3, r = 0.01 +/- 0.23, P = 0.48). By contrast, a significant negative force-frequency relation was seen during incremental atrial pacing after verapamil (slope = -4.1 +/- 1.3, r = -0.80 +/- 0.23, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1987

Effects of nifedipine on diastolic function during brief periods of flow-limiting ischemia in the conscious dog.

To determine the contribution of transsarcolemmal calcium flux to abnormal diastolic function produced by brief periods of flow-limiting ischemia and reperfusion, we evaluated early and late diastolic function during transient coronary occlusion and reperfusion before and during administration of intravenous nifedipine (NIF) (10 +/- 1 microgram/kg/min) in nine preinstrumented conscious dogs. We also assessed the effects of nitroprusside (NTP) (2 +/- 0.2 micrograms/kg/min) during an identical period of ischemia and reperfusion to independently assess the consequences of altered loading alone on diastolic function. To minimize the effects of temporal dysynchrony and altered ventricular loading conditions on isovolumetric relaxation, we developed a conscious dog preparation of reversible transient (30 to 60 sec) bilateral coronary occlusion (BCO). BCO was characterized by significant systolic depression: maximum (+)dP/dt decreased (from 2617 +/- 600 to 1981 +/- 565 mm Hg/sec, p less than .05), left ventricular transverse dimension shortening diminished (from 20 +/- 5 to 9 +/- 5%, p less than .05), and the left ventricle dilated (42.4 +/- 6.4 to 43.8 +/- 6.3 mm, p less than .05). Concomitantly the time constants of isovolumetric relaxation prolonged (from 22 +/- 3 to 28 +/- 4 msec, p less than .05) and minimal diastolic left ventricular pressure increased (from -3 +/- 6 to 6 +/-6 mm Hg, p less than .05). The passive diastolic pressure-dimension relationship shifted upward and to the right and was associated with increased chamber stiffness (from 0.50 +/- 0.26 to 1.03 +/- 0.53 mm Hg/mm, p less than .05) and increased left ventricular end-diastolic pressure (from 7 +/- 7 to 19 +/- 7 mm Hg, p less than .05). Reperfusion immediately after BCO was characterized by prompt restoration of systolic contractile performance [maximum (+)dP/dt 3220 +/- 530 mm Hg/sec] but persistently abnormal early and late diastolic function (time constant of isovolumetric relaxation 30 +/- 6 msec, left ventricular end-diastolic pressure 20 +/- 7 mm Hg). The effects of drug administration on ventricular function during BCO were then evaluated under matched loading conditions. NTP improved time constant of isovolumetric relaxation (20 +/- 8 vs 28 +/- 4 msec, p less than .05) and minimal diastolic left ventricular pressure (2 +/- 5 vs 6 +/- mm Hg, p less than .05) during BCO, but NIF did not (time constant of isovolumetric relaxation 27 +/- 6 msec, minimal diastolic left ventricular pressure 7 +/- 5 mm Hg).(ABSTRACT TRUNCATED AT 400 WORDS)

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