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Cited by 40Heart Failure Treatment and ManagementRenin-Angiotensin System StudiesCardiovascular and exercise physiology

Angiotensin converting enzyme inhibition, AT1 receptor inhibition, and combination therapy with pacing induced heart failure: effects on left ventricular performance and regional blood flow patterns

Krombach, R·1998·Cardiovascular Research
DOI 10.1016/s0008-6363(98)00050-9
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Abstract

BACKGROUND: AT1 receptor activation has been demonstrated to cause increased vascular resistance properties which may be of particular importance in the setting of congestive heart failure (CHF). The overall goal of this study was to examine the effects of ACE inhibition (ACEI) alone, AT1 receptor blockade alone and combined ACEI and AT1 receptor blockade on LV pump function, systemic hemodynamics and regional blood flow patterns in the normal state and with the development of pacing induced CHF, both at rest and with treadmill induced exercise. METHODS AND RESULTS: Pigs (25 kg) were instrumented in order to measure cardiac output (CO), systemic (SVR) and pulmonary vascular (PVR) resistance, neurohormonal system activity, and myocardial blood flow distribution in the conscious state and assigned to one of 4 groups: (1) rapid atrial pacing (240 bpm) for 3 weeks (n = 7); (2) ACEI (benazeprilat, 3.75 mg/day) and pacing (n = 7); (3) AT1 receptor blockade (valsartan, 60 mg/day) and rapid pacing (n = 7); and (4) ACEI and AT1 receptor blockade (benazeprilat/valsartan, 1/60 mg/day, respectively) and pacing (n = 7). Measurements were obtained at rest and with treadmill exercise (15 degrees, 3 miles/h; 10 min) in the normal control state and after the completion of the treatment protocols. With rapid pacing, CO was reduced at rest and with exercise compared to controls. ACEI or AT1 blockade normalized CO at rest, but remained lower than control values with exercise. Combination therapy normalized CO both at rest and with exercise. Resting SVR in the CHF group was higher than controls and SVR fell to a similar degree with exercise; all treatment groups reduced resting SVR. With exercise, SVR was reduced from rapid pacing values in the ACEI and combination therapy groups. PVR increased by over 4-fold in the rapid pacing group both at rest and with exercise, and was reduced in all treatment groups. In the combination therapy group, PVR was similar to control values with exercise. Plasma catecholamines and endothelin levels were increased by over 3-fold with chronic rapid pacing, and were reduced in all treatment groups. In the combination therapy group, the relative increase in catecholamines and endothelin with exercise were significantly blunted when compared to rapid pacing only values. LV myocardial blood flow at rest was reduced in the rapid pacing only and monotherapy groups, but was normalized with combination therapy. CONCLUSION: These findings suggest that with developing CHF, combined ACE inhibition and AT1 receptor blockade improved vascular resistive properties and regional blood flow distribution to a greater degree than that of either treatment alone. Thus, combined ACEI and AT1 receptor blockade may provide unique benefits in the setting of CHF.

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  • Swine have a large heart rate reserve, increasing from approximately 89-117 bpm at rest to 259-306 bpm during exercise.

    “Swine have a large heart rate reserve as they can increase their heart rates from approximately 89–117 bpm at rest to 259–306 bpm during exercise (Armstrong, Delp, Goljan, & Laughlin, 1987; Delp, et al., 2001; Krombach, et al., 1998; Roth, et al., 1990).”

    From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Krombach, et al., 1998

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Authors
Krombach, R.
Affiliations
Medical University of South Carolina (US)
Corresponding author
Krombach, R
Venue
Cardiovascular Research
Publisher
Oxford University Press (OUP)
Published
1998-06
Volume
38
Issue
3
Pages
631-645
ISSN
0008-6363 (ISSN-L)
DOI
10.1016/s0008-6363(98)00050-9
OpenAlex
W2169516159
Cited by
40
References
65
Citations by year
2016: 1 · 2013: 1
FWCI
4.79
Type
journal article
Language
en
Open access
closed
Locations
  • Cardiovascular Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1r29hl045024-01a1)
  • National Heart, Lung, and Blood Institute (HL45024, HL-56603, R01HL056603)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords
angiotensin-converting enzyme inhibition, AT1 receptor blockade, valsartan, benazeprilat, combination therapy, left ventricular pump function, regional myocardial blood flow, systemic vascular resistance, pulmonary vascular resistance, catecholamines, endothelin, neurohormonal activation, exercise hemodynamics, atrial pacing, congestive heart failure
MeSH terms
Valsartan, Angiotensin I, Angiotensin-Converting Enzyme Inhibitors, Animals, Benzazepines, Cardiac Pacing, Artificial, Epinephrine, Physical Exertion, Heart Failure, Hemodynamics, Male, Norepinephrine, Regional Blood Flow, Renin, Swine, Tetrazoles, Valine, Endothelins, Ventricular Function, Left, Angiotensin Receptor Antagonists

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