Related Experiment Videos
Regression of ventricular hypertrophy abolishes cardiocyte vulnerability to acute hypoxia
1Department of Anatomy, University of Iowa, Iowa City 52242.
Insights
Left ventricular hypertrophy (LVH) increases heart vulnerability to hypoxia. Regression of LVH with captopril treatment improved resistance to hypoxic damage in spontaneously hypertensive rats.
Area of Science:
- Cardiovascular Physiology
- Pathology
- Pharmacology
Background:
- Left ventricular hypertrophy (LVH) from pressure overload impairs myocardial perfusion and oxygen delivery.
- This can lead to cardiocyte intracellular damage and increased vulnerability to hypoxia.
- Understanding LVH regression's impact on hypoxic tolerance is crucial.
Purpose of the Study:
- To test if reduced LVH and normalized coronary flow minimize the hypertrophied left ventricle's vulnerability to acute hypoxia.
- To evaluate the effects of antihypertensive treatments on LVH regression and hypoxic tolerance.
Main Methods:
- Spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats received captopril or hydralazine/hydrochlorothiazide for 3 months.
- Rats were subjected to acute hypoxia (7% O2) for 20 minutes.
- Hemodynamics, blood gases, pH, and cardiac ultrastructure via electron microscopy were analyzed.
Main Results:
- Both treatments lowered blood pressure; only captopril reduced heart mass.
- Hypoxia similarly affected hemodynamics and blood gases across all groups.
- Hypertrophied ventricles showed significant hypoxic damage (T-tubular swelling, edema, mitochondrial changes); non-hypertrophied ventricles were largely unaffected.
Conclusions:
- LVH exacerbates hypoxic myocardial damage.
- Captopril-induced LVH regression improved tolerance to acute hypoxia.
- Targeting LVH regression may be a strategy to protect the heart during hypoxic stress.
Abstract:
Left ventricular hypertrophy (LVH) secondary to a pressure overload commonly leads to perfusion abnormalities that may limit oxygen delivery to the myocardium and, therefore, result in cardiocyte intracellular damage. We initiated this study to test the hypothesis that the increased vulnerability of the hypertrophied left ventricle to acute hypoxia is minimized when LVH regresses and maximal coronary flow returns to normal. Six-month-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were divided into control or one of two antihypertensive treatment groups. A 3-month treatment consisted of captopril (75-100 mg/kg) or hydralazine (80-160 mg/L) with hydrochlorothiazide (500 mg/L) added to each therapy. At the conclusion of the treatment period, the rats were administered a 7% O2-93% N2 gas mixture for 20 minutes to induce acute hypoxic stress during which time hemodynamics, blood gases, and pH were monitored. The heart was then rapidly fixed by vascular perfusion and prepared for electron microscopy. Captopril and hydralazine were equally effective in lowering arterial pressure in both strains, but only captopril was efficacious in reducing heart mass. Hypoxia-induced changes in hemodynamics, blood gases, and pH were similar in all of the groups; PO2 was decreased by about 70%. The electron micrographs revealed that the hypertrophied left ventricle consistently showed morphologic evidence of hypoxic damage (as indicated by T-tubular swelling, intracellular edema, and mitochondrial alterations); in contrast hypoxia had little effect on the non-hypertrophied ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)