JOURNAL TRANSCRIPT
The Peripheral Vascular Response to Severe Exercise in Untethered Dogs before and after Complete Heart Block SnTEEN F. VATNBi, CHARLms B. HiGGINs, SAXON WHITE, THOMAS PATRICK, and DEAN FRAN.KLN with the technical assistance of DAmEL P. McKOWN From the Department of Medicine, University of California, San Diego, and Scripps Clinic and Research Foundation, La Jolla, California 92037
A B S T R A C T The peripheral vascular response to severe exercise was studied in 11 healthy conscious dogs instrumented with Doppler ultrasonic flow probes on the mesenteric, renal, and iliac arteries, and miniature pressure gauges in the aorta. The response to severe exercise was restudied in six of these dogs after recovery from a second operation producing complete heart block by the injection of formalin into the atrioventricular (AV) node. Three of these dogs also exercised while their ventricles were paced at rates of 100/min and 200/min. The untethered normal dogs ran at speeds of 15-25 miles/hr behind a mobile recording unit for a distance averaging 1.5 miles, while continuous measurements of arterial blood pressure and blood flow were telemetered and recorded on magnetic tape. Severe exercise in normal dogs increased heart rate from 84 to 259/min, arterial pressure from 89 to 140 mm Hg, flow resistance in the mesenteric and renal beds by 59 and 52% respectively, and iliac blood flow 479% above control, while mesenteric and renal blood flows remained constant and iliac resistance decreased by 73%. In dogs with complete AV block, severe exercise at speeds of 10-18 miles/hr increased heart rate from 47 to 78/min, mean arterial pressure from 81 to 89 mm Hg, iliac flow 224%, resistance in the renal bed by 273%, and mesenteric bed by 222% while it decreased blood flow in mesenteric and renal beds by 61 and 65% respectively, and iliac resistance by 62%. A similar response occurred during exercise with pacing at 100/min, This work was presented in part before the 43rd Scientific Sessions of the American Heart Association in Atlantic City, N. J., November 1970. Dr. Higgins is a Surgical Scholar supported by U. S. Public Health Service Grant GM 01559. Dr. White was an Overseas Research Fellow of the Life Insurance Medical Research Fund of Australia and New Zealand. Received for publication 7 January 1971 and in revised form 31 March 1971.
1950
but when paced at 200/min a more normal exercise response reappeared. Thus, in normal dogs the peripheral vascular response to severe exercise involved increases in heart rate, arterial pressure and visceral resistance but visceral blood flow did not decrease. In dogs with heart block, where the ability to increase heart rate is severely compromised, compensatory reduction of mesenteric and renal blood flows occurred. INTRODUCTION The primary cardiovascular adjustment to severe exercise involves an increase in cardiac output to provide increased blood flow to the working muscles. In addition, the visceral vascular beds are thought to respond to severe exercise with sufficient increases in resistance to reduce blood flow in the mesenteric and renal circulations (1-8), thereby diverting blood flow from the inactive viscera to the exercising musculature. Although this latter mechanism is teleologically appealing, direct measurements of regional blood flows in healthy conscious animals during exercise have indicated that this compensatory mechanism does not occur, i.e., blood flow to the kidney and gut do not decrease (9-11). However, it is conceivable that this peripheral mechanism is potentially available and although not apparent in the normal animals, could be revealed if the central adjustment to exercise were impaired, e.g., by preventing the increase in heart rate during exercise. Accordingly, in the present investigation, 11 normal, healthy, untrained mongrel dogs were studied during severe exercise and 6 of these dogs were restudied during severe exercise when the increase in heart rate occurring normally during exercise was limited by the presence of surgically-induced complete heart block. In order to obtain a response to exercise free from the impediments of cables, tethers, treadmills, and the laboratory environment, measurements of blood flow and blood pressure
The Journal of Clinical Investigation Volume 50 1971
FIGURE 1 One of the instrumented dogs running at 22 miles/hr behind the mobile recording unit. The FM signal containing the flow-pressure data is telemetered from the instruments carried by the dog in saddlebags (insert) and received by the antenna on the bus, which in turn is coupled to the recording instruments. were telemetered from the untethered dogs as they ran behind a mobile recording unit over level and graded terrain for distances averaging 1.5 miles and at speeds of 15-25 miles/hr. This study was designed first to elucidate the peripheral vascular response to severe exercise in the normal animal and specifically to determine the extent to which shunting of visceral flow occurred. In addition, we determined the peripheral circulatory adjustments to severe exercise when the central cardiac response, i.e., the increase in heart rate, was limited.
METHODS Mongrel dogs weighing between 22 and 36 kg were operated upon using Na pentobarbital, 30 mg/kg and sterile surgical technique. Doppler ultrasonic blood-flow transducers (12) were implanted around the cranial mesenteric, left renal and left iliac arteries, and miniature pressure gauges' (13) were implanted in the thoracic or abdominal aorta. Complete heart block was produced during a second operation using a right thoracotomy incision and Na pentobarbital anesthesia, 30 mg/kg. The atrioventricular (AV) node was destroyed by injection of 0.1-1.0 cc of 37% formalin with a 23 gauge 'Konigsberg P22; Konigsberg Instruments, Inc, Pasadena, Calif.
needle positioned in the area of the AV node by palpation through the right atrium. Complete heart block was confirmed by electrocardiogram. Pacemaker electrodes fabricated from multistranded copper wire were sutured to the right ventricle during the latter operation. The dogs were paced during recovery using a Medtronic pacemaker.' On the first postoperative day, the pacemaker rate was turned down from 140/min to 100/min and kept there for 1-4 wk until the dogs had recovered from the operation. The experiments were conducted in 11 normal, healthy mongrel dogs 2-6 wk after recovery from implantation of blood flow probes and blood pressure gauges, and in 6 of these dogs 1-4 wk after recovery from the second operation at' which complete heart block was induced. The protocol for the experiments was as follows. The dogs were taken to isolated roads and allowed to recline at rest while control records of blood flow and arterial pressure were recorded. The dogs were allowed to stand 1-3 min before exercise. Then the mobile unit carrying the electronic recording equipment drove off. The dogs ran behind the van at speeds of 15-25 miles/hr over level and graded roads for distances averaging 1.5 miles and ranging up to 6 miles (Fig. 1). Occasionally the dogs would stop briefly to 'urinate, or defecate, or chase a squirrel. The level of exercise attained by the dogs in heart block was slightly lower, running at speeds of 10-18 miles/hr. Two of these dogs exercised a Medtronic, Inc. Minneapolis, Minn.
Blood Flow Distribution during Severe Exercise
1951
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FIGURE 4 Record from a normal dog reclining, then standing, then running at an average speed of 18 miles/hr, and the subsequent recovery from exercise immediately and at 15, 30, and 45 min later. The phasic waveforms and mean values for renal blood flow and arterial pressure, heart rate, and computed mean renal resistance are shown. In this case renal blood flow actually increased slightly during severe exercise.
value of 89 ±4 to 140 ±5 mm Hg during severe exercise (Fig. 2). In contrast with the response of heart rate, the increase in pressure occurred gradually and was often not observed until after the 1st min of severe exercise. Pressure remained elevated at a generally constant value as long as the dogs did not decrease their level of exerLYING ILIAC BLOOD FLOW VELOCITY cm/sec IA ME AN
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cise (Figs. 3-5). During recovery from exercise pressure gradually returned to preexercise control values during the subsequent 45 min. In six dogs with complete heart block, reclining at rest, mean arterial pressure was 81 ±3 mm Hg as compared with 89 ±4 mm Hg for the normal dogs. The
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