Abstract
BackgroundCoronary flow reserve (CFR) is used as a measure of coronary endothelial function. We investigated the effect of increased afterload on CFR of pregnant and non-pregnant rats.MethodsAfterload increase in Wister rats (both pregnant and non-pregnant) was achieved by the infusion of angiotensin II (Ang II) for ∼10 days or by subjecting them to transverse aortic constriction (TAC) for ∼14 days. Control groups were infused with 0.9% NaCl or had sham surgery, respectively. In pregnant rats, the experiments were performed close to term gestation. Doppler velocity waveforms of the left main coronary artery were recorded using a high resolution ultrasound imaging system (Vevo 770, VisualSonics, Canada) at baseline while the animals were anesthetized with 1.5% inhaled isoflurane, and during maximal coronary dilatation obtained by the inhalation of 3.5% of isoflurane. CFR was calculated as the ratio between the peak coronary flow velocities (CFRpeak) and the velocity-time integrals (CFRVTI) recorded at hyperemia and at baseline.ResultsCFR could be calculated in 60 of 75 (80%) animals. There were no differences in CFR between intervention and control groups irrespective of whether afterload was increased by Ang II or TAC. In the TAC-study CFRpeak (1.54±0.07 vs 1.85±0.17; p = 0.03) was decreased in pregnant compared to non-pregnant shams. When sham animals from both studies were pooled together both CFRpeak (1.42±0.07 vs 1.86±0.16; p = 0.005) as well as CFRVTI (1.45±0.07 vs 1.78±0.12; p = 0.03) were significantly lower in pregnant rats compared to non-pregnant.ConclusionsCFR can be measured non-invasively in rats using Doppler echocardiography and high concentrations of inhaled isoflurane as a coronary vasodilator. In pregnant rats, CFR is reduced close to term. CFR is not affected by increased left ventricular afterload caused by chronic Ang II infusion or TAC.
Highlights
Coronary flow reserve (CFR), i.e. the ratio of maximum to baseline coronary blood flow [1], is used as a measure of coronary endothelial function
In the transverse aortic constriction (TAC)-study echocardiography was performed by one operator (N.T.S.) in all animals
CFR measurements from 32 (76%) animals were eligible for analysis; 10 pregnant sham, 7 pregnant TAC, 7 non-pregnant sham, and 8 non-pregnant TAC
Summary
Coronary flow reserve (CFR), i.e. the ratio of maximum to baseline coronary blood flow [1], is used as a measure of coronary endothelial function. Human studies have shown a link between impaired coronary microvascular function and adverse cardiovascular events [2,3]. In order to measure CFR, application of an agent with potent endothelium independent vasodilating properties is needed. Inhaled isoflurane, which is used as an anaesthetic in small animal research, is a potent coronary vasodilator. Hartley et al have shown that the increase in coronary blood flow after administering high concentrations of inhaled isoflurane can be used to estimate CFR in mice [9,10]. Coronary flow reserve (CFR) is used as a measure of coronary endothelial function. We investigated the effect of increased afterload on CFR of pregnant and non-pregnant rats
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