Increased ejection fraction produced by a long-term subhypertensive infusion of norepinephrine in the conscious dog

Laks, Michael M.; Garner, Daniel; Wong, Victor K.

doi:10.1016/0002-8703(79)90471-x

Cited by 10 publications

(3 citation statements)

References 16 publications

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“…Yet, despite the absence of hypertension, LV weight and wall thickness increased while RV weight remained unchanged. Subsequently, Laks and his colleagues 23 reported increases in stroke volume and ejection fraction at 3 months, as measured using left ventriculography. These studies are difficult to interpret, since infusions were stopped 30 minutes before angiographic study.…”

Section: Discussionmentioning

confidence: 98%

“…Left ventricular (LV) pressure was measured with the solid-state miniature pressure gauge, which was calibrated in vitro against a mercury manometer and in vivo against the arterial and left atrial pressure measurements. An ultrasonic transit-time dimension gauge 23 was used to measure LV diameter. This instrument generates a voltage linearly proportional to the transit time of acoustic impulses traveling at the sonic velocity of 1.5 x 10* m/sec between the previously implanted 3-MHz piezoelectric crystals, thus giving a continuous record of LV diameter.…”

Section: Methodsmentioning

confidence: 99%

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Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs.

King¹,

Sack²,

Kichuk³

et al. 1987

Hypertension

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SUMMARY To better define the mechanisms of blood pressure control in states of catecholamine excess, we infused norepinephrine for 28 days using subcutaneously implanted osmotic pumps in dogs previously instrumented for monitoring left ventricular dynamics and cardiac output. Plasma norepinephrine rose from 238 ± 27 to 4346 ± 952 pg/ml at 21 days, while epinephrine and dopamine levels did not change. Heart rate fell from 85 ± 4 to 63 ± 6 beats/min, while arterial pressure was unchanged from baseline. Total peripheral resistance rose 0.011 ± 0.003 mm Hg/ml/min from a control value of 0.029 ± 0.002 mm Hg/ml/min, and cardiac output decreased 1093 ± 292 ml/min from a baseline level of 3575 ± 156 ml/min. Since stroke volume did not change, the maintenance of arterial pressure is related to decreases in cardiac output secondary to bradycardia. Buffering mechanisms are responsible for maintenance of systemic arterial pressure because hexamethonium and atropine caused hypertension. Although left ventricular end-diastolic pressure, end-diastolic diameter, shortening, rate of change of pressure, velocity of myocardial shortening, cardiac work, stroke work, and the double product did not change significantly during the study, postmortem examination demonstrated biventricular hypertrophy. Thus, despite markedly elevated catecholamine levels and no elevation of systemic arterial pressure, myocardial hypertrophy developed. These studies lend support to the hypothesis that norepinephrine may be a direct myocardial tropic hormone and suggest that intense activation of reflex buffering mechanisms maintains blood pressure in the normal range during chronic catecholamine infusion. (Hypertension 9: 582-590, 1987) KEY WORDS • bradycardia • hypertension • hypertrophy • catecholamines • total peripheral resistance • atropine E LEVATIONS in catecholamine levels may be associated with a number of disease states, including mitral valve prolapse (MVP), 1 -2 chronic myocardial failure, 3 " 6 and pheochromocytoma. 7 These disease states may be characterized by sustained or episodic hypertension, myocardial dysfunction, and cardiomyopathy.Recently, it has been noted that certain patients with MVP, chronic myocardial failure, or pheochromocytoma have dysautonomia, manifested by abnormalities in heart rate or blood pressure response (or both) to orthostatic change or exercise. 8 " 12 Some investigations of patients with MVP having dysautonomia are consistent with evidence of hyperadrenergic states and some with simultaneous hypervagatonia. 9 -13 Significant elevations in serum catecholamine levels have been observed in a group of symptomatic patients with MVP 1 ' l4 ; these results have been confirmed by other workers. 2 ' 8> l5 Patients with chronic myocardial failure, regardless of etiology, have elevated plasma norepinephrine (NE) levels. 16 In addition, defects in baroreceptor reflex-mediated vasoconstrictor responses have been noted in dogs 17 and in patients 18 -19 with marked myocardial dysfunction.Several studies, summarized by Ec...

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs.

King¹,

Sack²,

Kichuk³

et al. 1987

Hypertension

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“…This is supported by the findings that prolonged infusion of norepinephrine not only produced myocardial hypertrophy (36), but also enhanced myocardial contractility in dogs (37), and that immunologic sympathectomy abolished the increase in heart to body weight ratio produced by chronic exercise in rats (38). In addition, like physical training, repeated injections of catecholamines cause an increased sensitivity to the metabolic effects of norepinephrine (39), which probably is responsible for the enhanced lipid oxidation in trained subjects during exercise (40).…”

Section: Resultsmentioning

confidence: 78%

Conditioning Effects of Chronic Infusions of Dobutamine

Liang¹,

Tuttle²,

Hood³

et al. 1979

J. Clin. Invest.

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A B S T R A C T We studied the conditioning effects ofchronic infusion of dobutamine and exercise training in three groups of chronically instrumented dogs. One group was infused with normal saline, a second group was infused with dobutamine (40 ,ug/kg per min), and the third group was exercised on a treadmill at 4 mph, up a 100 incline. Each group was either infused or exercised for 2 h a day, 5 d a week for 5 consecutive wk. Resting heart rate and arterial blood lactate concentration, measured at weekly intervals, decreased progressively in the dobutamine and exercise groups, but not in the group that received normal saline infusion. Cardiovascular responses to submaximal treadmill exercise were not changed by 5 wk of normal saline infusion. However, the increases in heart rate, cardiac output, mean aortic blood pressure, arterial blood lactate, plasma renin activity, and norepinephrine concentration during exercise were significantly smaller after 5 wk of conditioning with either dobutamine or exercise training. After conditioning, the increases in arteriovenous oxygen difference during exercise were larger in the latter two groups, but the increases in total body oxygen consumption did not differ before and after conditioning.To assess ventricular function, we intravenously infused methoxamine both before and after conditioning. The slope of the line that related systolic aortic blood pressure and mean left atrial pressure increased in the animals conditioned with either dobutamine or exercise, indicating enhanced myocardial contractility. Left ventricular blood flow was lower in these two groups of animals than it was in the normal saline group. Left ventricular weight did not differ among the three groups.Our results show that chronic infusion of dobutamine produced cardiovascular and metabolic conditioning effects like those produced by exercise training, and further suggest that sympathetic stimulation during exercise plays a role in physical conditioning.

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Effects of chronic infusion of norepinephrine on cardiac structure, function, and biochemistry: Physiologic versus pathologic hypertrophy

Laks

2009

Clin Cardiol

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Ventricular hypertrophy should be divided into at least physiologic and pathologic states in order to clarify structural and functional clinical alterations. The elucidation of the structural, functional, and biochemical mechanisms of ventricular hypertrophy is vital to designing effective preventive and therapeutic measures for the hypertensive patient. Tissue markers may help differentiate pathologic from physiologic hypertrophy. Studies have established the concept that norepinephrine may be a myocardial cellular hypertrophying hormone. The studies ranged from the direct application of norepinephrine to isolated myocardial cells to the chronic subhypertensive infusion of norepinephrine into the conscious, free‐roaming dog. Norepinephrine infusion can produce physiologic ventricular hypertrophy or a pathologic state of hypertrophic cardiomyopathy, the former by a three‐ to four‐month infusion and the latter by an infusion of more than six months. The biochemical effect of subhypertensive infusion of norepinephrine was studied prior to the production of ventricular hypertrophy, thereby permitting the elucidation of the mechanism of the hypertrophic process. The biochemical stimulus for the production of myocardial cellular hypertrophy is postulated to be a diminution of cyclic AMP and a stimulation of alpha‐1 receptors. Because the ventricular septum has the highest content of adenylate cyclase, which does not increase with cyclic AMP, these changes are postulated to be the biochemical basis for septal hypertrophy in the disease entity hypertrophic cardiomyopathy. A unique conscious‐canine model for the production of a myocardial infarction capable of creating a controlled localized occlusion of the coronary artery is presented. By using two‐dimensional echocardiography in the conscious dog, we demonstrated that the noninfarcted left ventricular muscle mass increases in proportion to the increase in a particular function as measured by ejection fraction. Post‐myocardial infarction hypertrophy can thus be considered a compensatory response and therefore physiologic hypertrophy.

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Increased ejection fraction produced by a long-term subhypertensive infusion of norepinephrine in the conscious dog

Cited by 10 publications

References 16 publications

Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs.

Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs.

Conditioning Effects of Chronic Infusions of Dobutamine

Effects of chronic infusion of norepinephrine on cardiac structure, function, and biochemistry: Physiologic versus pathologic hypertrophy

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