Inhibition of Angiotensin-Converting Enzyme Reduces Susceptibility of Hypertrophied Rat Myocardium to Ventricular Fibrillation.

Shimada, Yasuyuki; Gunasegaram, Suba; Yokoyama, Hiroyuki; Avkiran, Metin

doi:10.1253/circj.66.1045

Cited by 9 publications

(20 citation statements)

References 61 publications

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“…1,2-5 Our previous study showed that left ventricular (LV) hypertrophy in the rat increases the animal's vulnerability to ventricular arrhythmias induced by LV ischaemia and reperfusion. 6 Impairment of the coronary circulation, therefore, may play a major role in the cardiac sudden death associated with LV hypertrophy. In the clinical setting, most cases of LV hypertrophy are mediated by systemic hypertension or valve disease, but it is not known if LV hypertrophy mediates coronary disorder and impairs both the left and right coronary circulation.…”

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Left and Right Coronary Circulation in Left Ventricular Hypertrophy. Effects of Angiotensin Converting Enzyme Inhibition.

Shimada

Avkiran

2002

Circ J

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n increasing number of clinical studies have revealed that cardiac hypertrophy is a powerful risk factor for sudden cardiac death, probably because of myocardial ischaemia. 1,2-5 Our previous study showed that left ventricular (LV) hypertrophy in the rat increases the animal's vulnerability to ventricular arrhythmias induced by LV ischaemia and reperfusion. 6 Impairment of the coronary circulation, therefore, may play a major role in the cardiac sudden death associated with LV hypertrophy. In the clinical setting, most cases of LV hypertrophy are mediated by systemic hypertension or valve disease, but it is not known if LV hypertrophy mediates coronary disorder and impairs both the left and right coronary circulation. A disorder of the right coronary circulation in the presence of LV hypertrophy should be considered, especially with regard to the treatment of ischemic heart disease. 7 In the rat LV pressure-overload model, LV hypertrophy is associated with impaired coronary circulation 8-13 that can be normalized by administration of an angiotensin converting enzyme (ACE) inhibitor. 11,12,14,15 In previous in vitro studies, [8][9][10][11][12][13] however, the total coronary flow rate (combined flow rate in the left and right coronary beds) was measured with a conventional Langendorff perfusion system in order to calculate the indices of coronary circulation, but such indices may reflect the mean of the left and right coronary beds, which could be very different from each other. The changes in coronary circulation that occur in the individual coronary arterial beds in LV hypertrophy have never been studied and are still unknown.The objectives of this study were to determine, in a rat model of pressure-overload LV hypertrophy, 16 (i) the changes that occur in coronary reserve in the left and right coronary arterial beds, with and without ACE inhibition, and (ii) the concomitant changes that occur in arterial pressure and LV mass. To achieve those objectives, we exploited the advantages of a dual coronary perfusion model 17 that enables independent perfusion of left and right coronary beds, which supply predominantly the hypertrophied LV and non-hypertrophied right ventricle, respectively. MethodsThis investigation was performed in accordance with the Home Office Guidance on the Operation of the Animals (Scientific Procedures) Act 1986, published by Her Majesty's Stationery Office, London. Induction of Aortic ConstrictionDetails of the surgical procedure have been described previously. 17 In brief, male Wistar rats (body weight, 170± 9 g) were anesthetized with Hypnorm (0.3 ml/kg body weight im) and diazepam (2.5 mg/kg body weight ip). Via a small abdominal incision, the aorta was isolated and cleared of surrounding tissue. A small titanium clip (Atrauclip, Rusch UK Ltd, High Wycombe, UK) was placed around the suprarenal aorta with specially adapted pliers set to a width of 0.45 mm. The incision was closed with vicryl and silk sutures and the rats were left to recover under a heating lamp. The rats were closely obs...

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Left and Right Coronary Circulation in Left Ventricular Hypertrophy. Effects of Angiotensin Converting Enzyme Inhibition.

Shimada

Avkiran

2002

Circ J

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“…21,22) In our animal model, however, the incidence of VF did not associate with impaired coronary reserve. 3,20) Therefore, the changes in coronary circulation did not contribute, at least in our model, to the increased susceptibility of ischemia/reperfusion arrhythmias.…”

Section: Mechanisms Of Increased Vulnerability To Ischemia-or Reperfumentioning

confidence: 70%

“…7,8) Our recent study with the same animal model has shown that local angiotensin converting enzyme (ACE) activity plays a key role in the increased susceptibility in LV hypertrophy. 3) We showed that intrinsic changes in hypertrophied myocardium such as the ratio of ANF mRNA to GAD mRNA were associated with the incidence of reperfusion VF.…”

Section: Mechanisms Of Increased Vulnerability To Ischemia-or Reperfumentioning

confidence: 89%

“…Throughout the experiment, each coronary bed was perfused at a constant pressure (equivalent to 75 mmHg) with oxygenated perfusion solution drawn from a temperature-regulated reservoir (37°C). The perfusion solution was of the following composition (in mmol/L): NaCl, 118.5; NaHCO 3 To maintain normal sinus rate and 1:1 atrium-ventricle (AV) conduction during regional ischemia (especially during right coronary bed ischemia), we employed a right intra-atrium superfusion technique. 8) That involved slightly enlarging the inferior vena caval orifice with a single fine scissor cut and carefully making a small hole in the right atrium away from the region of the sinoatrial node.…”

Section: Dual Coronary Perfusion Of Isolated Rat Hearts With Right Inmentioning

confidence: 99%

“…1) Several animal studies 2,3) have demonstrated a powerful association between LV hypertrophy and fatal ventricular arrhythmias induced by ischemia and reperfusion. The increased risk of sudden cardiac death in patients with LV hypertrophy may be due to an increased susceptibility to ventricular arrhythmias.…”

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Susceptibility to Ischemia and Reperfusion Arrhythmias in Myocardial Hypertrophy Due to Flow of Injury Current?

Shimada

Avkiran

2003

Jpn Heart J

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SUMMARYLeft ventricle (LV) hypertrophy is associated with an increased risk of sudden death, which may be due in part to a greater vulnerability to severe ventricular arrhythmias. Our objectives were to determine (i) whether pressure overload-induced LV hypertrophy increases susceptibility to ischemia-and/or reperfusion-induced ventricular fibrillation (VF), and (ii) whether any increased susceptibility is mediated by changes intrinsic to the hypertrophied myocardium. LV pressure overload was induced in rats by abdominal aortic constriction (AC), while controls received sham-operations (SH). Three weeks after the operation, LV weight was 44 ± 3% greater in AC rats than in SH rats although right ventricle (RV) weights were similar. At this time, isolated hearts (n = 12/group) were subjected to dual coronary perfusion. After 15 minutes of aerobic perfusion, either the left or right coronary bed (supplying predominantly LV or RV tissue, respectively) was subjected to 7 minutes of zero-flow ischemia and either 5 minutes of reperfusion (reperfusion study) or 40 minutes of sustained ischemia (ischemia study). AC rats exhibited greater susceptibility than SH rats to both ischemia-and reperfusion-induced ventricular fibrillation, but only when the hypertrophied LV was subjected to ischemia. The increased susceptibility to arrhythmias was not entirely due to a larger ischemic zone, indicating that intrinsic changes within hypertrophied myocardium played a role in arrhythmogenesis. (Jpn Heart J 2003; 44: 989-1004)

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Hypertrophieregression als Therapieprinzip des Hochdruckherzens

Hennersdorf

Schannwell

Schwartzkopff

et al. 2003

Herz

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PATHOPHYSIOLOGY AND THERAPY: Left ventricular hypertrophy represents an important factor determining the prognosis of hypertensive patients. Hypertrophy as identified by electrocardiography (Table 1) or echocardiography (Table 2) characterizes patients with a significantly increased risk of mortality and arrhythmia. From the pathophysiological point of view this is based on hypertrophy of the media in resistance vessels, on interstitial fibrosis, on a reduced coronary flow reserve and on the occurrence of ischemia (Figure 1). The diastolic and (later) systolic function of the heart are disturbed (Figures 2 to 4). Antihypertensive therapy with beta blockers and diuretics leads to a reduction of left ventricular mass by 5-8%, with ACE-inhibitors and AT-blockers by 13% (Figure 5). Particularly ACE-inhibitors can effectively reverse of the above mentioned pathological processes. Regression of hypertrophy goes along with an improved prognosis and a reduction of atrial and ventricular arrhythmias (Figure 6). A symptomatic treatment of arrhythmias should always be accompanied by medical therapy aimed at regression of hypertrophy. Optimal therapy results in normalizes of blood pressure, leads to a regression of hypertrophy and induces cardiac reparation, which in turn improve left ventricular function, reduces microvascular ischemia stress and arrhythmias. These therapeutic desiderates are also pertinent for hypertensive heart disease in the prehypertrophic state, as in juvenile hypertension.

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Inhibition of Angiotensin-Converting Enzyme Reduces Susceptibility of Hypertrophied Rat Myocardium to Ventricular Fibrillation.

Cited by 9 publications

References 61 publications

Left and Right Coronary Circulation in Left Ventricular Hypertrophy. Effects of Angiotensin Converting Enzyme Inhibition.

Left and Right Coronary Circulation in Left Ventricular Hypertrophy. Effects of Angiotensin Converting Enzyme Inhibition.

Susceptibility to Ischemia and Reperfusion Arrhythmias in Myocardial Hypertrophy Due to Flow of Injury Current?

Hypertrophieregression als Therapieprinzip des Hochdruckherzens

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