Duration Of Pressure Overload Research Articles

Cardiac hypertrophy or failure? - A systematic evaluation of the transverse aortic constriction model in C57BL/6NTac and C57BL/6J substrains.

BackgroundThe mouse model of transverse aortic constriction (TAC) has been widely used as a cardiac stress in the investigation of the molecular mechanisms of cardiac hypertrophy. Recently, the International Knockout Mouse Consortium has selected the C57BL/6NTac (BL/6N) mouse strain to generate null alleles for all mouse genes; however, a range of genetic and cardiac phenotypic differences have been reported between this substrain and the commonly used C57BL/6J (BL/6J) substrain. It has been reported by Garcia-Menendez and colleagues that 12-week C57BL/6NTac mice are susceptible to heart failure but little is known about the cardiac remodeling in this substrain as cardiac function progresses from compensation to decompensation.MethodsBL/6J and BL/6N mice were subjected to pressure overload via TAC. The impact of both age and duration of cardiac pressure overload induced by TAC on cardiac remodelling were systematically assessed.ResultsOur data showed that BL/6N mice developed eccentric hypertrophy with age- and time-dependent deterioration in cardiac function, accompanied by considerable interstitial fibrosis. In contrast, BL/6J mice were more resilient to TAC-induced cardiac stress and developed variable cardiac phenotypes independent of age and the duration of pressure overload. This was likely due to the greater variability in pre-TAC aortic arch dimension as measured by echocardiography. In addition to increased expression of brain natriuretic peptide and collagen gene type 1 and 3, BL/6N mice also had greater angiotensin II type 2 receptor (AT2R) gene expression than BL/6J counterparts at baseline and after 2-weeks TAC, which may contribute to the exacerbated interstitial fibrosis.ConclusionsBL/6N and BL/6J mice have very different responses to TAC stimulation and these differences should be taken into consideration when using the substrains to investigate the mechanisms of hypertrophy and heart failure.

Role of myocardial hypertrophy on acute and chronic right ventricular performance in relation to chronic volume overload in a porcine model: Relevance for the surgical management of tetralogy of Fallot

The age for correction of tetralogy of Fallot has progressively declined to the postnatal period, often despite an increased rate of transannular patch repair. However, the long-term effect of premature exposure to chronic pulmonary insufficiency on the right ventricle remains unknown. On the basis of the relationship between the duration of pressure overload and age, the role of previous pressure load-related hypertrophy on right ventricular (RV) performance after chronic volume overload was investigated in a porcine model. RV hypertrophy (RVH), induced by pulmonary artery banding, was studied in pigs with (RVH plus pulmonary insufficiency [PI]) and without (RVH) subsequent PI. The effect of volume overload was compared between these 2 groups and pigs without RVH but with PI and controls (sham). Both acute and chronic effects on RV function were studied using conductance technology and validated using echocardiography. After chronic volume overload, the end-systolic and end-diastolic volumes were smaller in the RVH+PI group than in the PI group, including a lower pulmonary regurgitation fraction (25% ± 5% vs 35% ± 5%; P = .002). RVH resulted in better preserved systolic function, confirmed by an increased preload recruitable stroke work slope (14.7 ± 1.8 vs 9.3 ± 1.3 Mw.s/mL; P = .025) and higher RV ejection fraction (51% ± 3% vs 45% ± 4%; P = .05). Myocardial stiffness was impaired in the RVH+PI group versus the PI group (β, 0.19 ± 0.03 vs 0.12 ± 0.02 mL(-1); P = .001), presenting restrictive physiology only in the condition associating RVH and PI. The results of the present study have demonstrated that RVH attenuates the RV remodeling process related to chronic PI. It enables better preservation of contractility but at the cost of sustained diastolic impairment. These findings might help to determine the timing and strategy for repair of tetralogy of Fallot when RV outflow tract morphology indicates a definite need for transannular reconstruction.

Preconditioning threshold of brief pressure overload of the left ventricle

BackgroundWe previously reported that pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits. The threshold of pressure overload was investigated in this study. MethodsPressure overload of the left ventricle was induced by partial snare of the ascending aorta in anesthetized, open-chest rabbits. Systolic left ventricular pressure (SLVP) was elevated 50% or 30% above baseline value by varying the degree of partial snaring. Different duration of pressure overload, including 10 minutes, 5 minutes, 3 minutes, or 2 minutes, was applied to determine the threshold of protective effects. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and reperfusions. Ten minutes after different pretreatment, 1 hour occlusion of the left anterior descending coronary artery followed by 3 hours reperfusion was done to induce MI. The size of area at risk and MI were determined by blue dye injection and triphenyl tetrazolium chloride staining after experiments. ResultsPressure overload increase of SLVP 50% above baseline value for 10 minutes, 5 minutes, and 3 minutes significantly reduced MI size (18.5 ± 3.6%, 21.4 ± 1.9% and 21.6 ± 1.7%, respectively, vs. 26.6 ± 1.0% in the control group, mean ± standard deviation, p < 0.01). A 30% increase of SLVP by pressure overload for 10 minutes, 5 minutes and 3 minutes also significantly decreased MI size (20.5 ± 2.5%, 21.6 ± 2.3%, and 21.5 ± 2.3%, p < 0.01). Ischemic preconditioning significantly decreased MI size (19.9 ± 2.8%, p < 0.001). Pressure overload to elevate SLVP 50% or 30% above baseline value for 2 minutes did not significantly alter MI size (25.0 ± 2.3% and 26.0 ± 1.7%, p = 0.122 and p = 0.457). Two episodes of 2 minutes pressure overload did not significantly decrease MI size (25.0 ± 2.2% and 25.5 ± 2.2%, p = 0.118 and p = 0.281). The hemodynamics, area at risk, and mortality were not significantly different among all groups of animals. ConclusionPressure overload to raise SLVP either 50% or 30% above baseline value reduced MI size. A minimum duration of 3 minutes was necessary to induce the protective effects.

A Rabbit Model to Study Regression of Ventricular Hypertrophy

The purpose of this study is to develop and characterise a reproducible rabbit model of LVH regression following pressure-induced myocardial hypertrophy. Without endotracheal intubation and mechanical ventilation, a median sternotomy was performed. The median incision was made exactly along the midline of the sternum. Ascending aortic diameter was reduced 50% above the aortic valve, which lead to an approximate 75% reduction in crosssectional area. The sham-operated rabbits underwent the same procedures without actual ligation of the aorta. The animals of early DB group and late DB group were subjected to the second operation for removing the ligation eight weeks or 16 weeks after the initial banding surgery, respectively. Echocardiography, haemodynamic assessment, histology, and electron microscopy were used to assess functional and structural aspects of myocardial hypertrophy at each time point. The pressure overload resulted in robust LVH assessed by echocardiography, haemodynamic assessment, LV weight/body weight ratios, histology, and electron microscopy. Ascending aortic debanding completely or partially reversed LVH. The degree of LVH regression was association with the duration of pressure overload, proved by the fact that restoration of LV structure and function was complete in animals subjected to eight weeks of aortic banding but incomplete in animals subjected to 16 weeks of aortic banding. The animals did not experience severe mechanical ventilatory impairment. These results demonstrate an efficient and reproducible method of promoting LVH regression in rabbits without endotracheal intubation and mechanical ventilation.

Regression of pressure overload-induced left ventricular hypertrophy in mice

As a prelude to investigating the mechanism of regression of pressure overload-induced left ventricular (LV) hypertrophy (LVH), we studied the time course for the development and subsequent regression of LVH as well as accompanying alterations in cardiac function, histology, and gene expression. Mice were subjected to aortic banding for 4 or 8 wk to establish LVH, and regression was initiated by release of aortic banding for 6 wk. Progressive increase in LV mass and gradual chamber dilatation and dysfunction occurred after aortic banding. LVH was also associated with myocyte enlargement, interstitial fibrosis, and enhanced expression of atrial natriuretic peptide, collagen I, collagen III, and matrix metalloproteinase-2 but suppressed expression of alpha-myosin heavy chain and sarcoplasmic reticulum Ca(2+)-ATPase. Aortic debanding completely or partially reversed LVH, chamber dilatation and dysfunction, myocyte size, interstitial fibrosis, and gene expression pattern, each with a distinct time course. The extent of LVH regression was dependent on the duration of pressure overload, evidenced by the fact that restoration of LV structure and function was complete in animals subjected to 4 wk of aortic banding but incomplete in animals subjected to 8 wk of aortic banding. In conclusion, LVH regression comprises a variety of morphological, functional, and genetic components that show distinct time courses. A longer period of pressure overload is associated with a slower rate of LVH regression.

Duration of pressure overload alters regression of coronary circulation abnormalities

Using a rat model of ascending aortic banding and debanding, we examined how the duration of pressure overload affects reversibility in coronary circulation abnormalities after relief of pressure overload. Four-week banding increased left ventricular dry weight-to-body weight ratio to 158 +/- 8% of that of sham-operated controls. In isolated nonworking hearts perfused with crystalloid solution, peak mean coronary flow rate (CFR) was measured after brief ischemia. CFR and CFR/dry tissue weight significantly decreased (75 +/- 5 and 54 +/- 3% of that of controls at 100 mmHg of coronary perfusion pressure; 75 +/- 5 and 54 +/- 4% at 150 mmHg, respectively). Four weeks after debanding was performed, CFR and CFR/dry tissue weight increased to similar levels in controls. On the other hand, 10-wk banding produced the same degree of myocardial hypertrophy and decreases in CFR and CFR/dry tissue weight as in 4-wk banded rats. Four weeks after debanding was performed, CFR had not changed. CFR/dry tissue weight increased because of regression of myocardial hypertrophy but was significantly lower than that in rats debanded after 4 wk of banding. Thus the duration of pressure overload does not affect the degree of coronary circulation abnormalities in the progression process but does affect it in the regression process.

Reversibility of the structural effects of pressure overload hypertrophy of cat right ventricular myocardium.

The purpose of the present quantitative structural study was to determine whether the histological alterations seen in pressure overloaded myocardium return to normal, as in vitro contractile function does, upon removal of the pressure overload stimulus. Three experimental groups of four cats each were studied: a group with pulmonary artery banding to create a pressure overload, a group that had been subjected to an equivalent duration of pressure overload and then had that pressure overload removed, and a group of sham-operated controls. Seven to 10 weeks after each operative procedure, the right ventricular pressure was elevated only in the pulmonary artery-banded group. The right ventricle/body weight ratio was significantly increased in the pressure overloaded group only. The body weight at sacrifice, the left ventricle/body weight ratio, and the right ventricular end-diastolic pressure did not differ significantly in the three groups. The striking histological changes in the right ventricular myocardium hypertrophing in response to a pressure overload were the decrease in the volume density of cardiocytes and the increase in connective tissue in papillary muscles. These were reversed when the pressure overload was removed. This study demonstrates that when a pressure overload is removed, myocardial structure returns to normal as the function returns to normal. Given the critical importance of the proportion of cardiocytes and connective tissue components to both systolic and diastolic cardiac function, these data support the hypothesis that the abnormal proportions of these structures provide a potential morphological basis for at least some of the functional abnormalities observed in pressure overload hypertrophy of the cat right ventricle.

Time-dependent alterations of myocardial microsomal yield and calcium accumulation in experimentally-induced right ventricular hypertrophy and failure

A preliminary study was designed to determine whether time-dependent alterations of cardiac microsomal yield and in vitro Ca 2+-accumulating activity occur during the development of pressure-overload-induced right vetricular hypertrophy (RVH). RVH was produced in cats by pulmonary artery banding, and they were killed 3 days (“early” RVH) or 30 or more days (“long-term” RVH) later. Microsomes were isolated by differential centrifugation of right ventricular free wall (RVFW) and left ventricular wall plus septum (LVS) homogenates. RVFW microsomal yield was significantly greater in 3-day RVH than in normal, sham-operated or long-term RVH cats. Under some experimental conditions, Ca 2+ accumulation by RVFW microsomes from RVH cats was significantly different from that seen in other groups; the duration of pressure overload did not alter maximum Ca 2+ accumulation significantly. RVFW microsomal Ca 2+ accumulation was markedly depressed in cats with RVH complicated by right ventricular failure. LVS microsomal yield and Ca 2+ accumulation were not altered significantly in any group. Our microsomal data suggests that in this model early RVH involves rapid compensatory synthesis of RVFW sarcoplasmic reticulum, with some increase in the ability of these membranes to accumulate Ca 2+. Inability to maintain compensated RVH, resulting in failure, appears to involve compromised Ca 2+ accumulation, but no apparent impairment of microsomal protein synthesis.