Masahito Miyagawa

The prevalence and prognostic significance of arrhythmias in Duchenne type muscular dystrophy

To investigate the prevalence and prognostic significance of cardiac arrhythmias in Duchenne type muscular dystrophy 24-hour ambulatory ECG was performed in 80 patients with Duchenne type muscular dystrophy, and they were followed up for 5 years. Various arrhythmias were observed in 63.8% (51 of 80) of the patients. Ventricular premature beats were found in 30% (24 of 80), and the incidence of ventricular premature beats increased as the clinical severity of skeletal muscle involvement advanced. Forty-seven patients survived for 5 years, but the incidence of arrhythmias increased from 38.3% (18 of 47) to 74.5% (35 of 47) (p < 0.001). During the 5-year period, four of 33 deaths were sudden. Malignant ventricular premature beats (ventricular couplets, ventricular tachycardia, and R-on-T-type ventricular premature beats) were observed in three of these four patients. It appears that cardiac arrhythmias are a common complication of Duchenne type muscular dystrophy and that the incidence of ventricular arrhythmias increases with the progression of myocardial involvement. There is an association between ventricular arrhythmias and sudden death, but the reduction of ventricular arrhythmias may not reduce the incidence of episodes of sudden death.

Cardioprotective effect of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) during acute ischemia-reperfusion injury in rats

MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, has the ability to stimulate prostacyclin release and to inhibit the lipoxygenase pathway in the arachidonic acid cascade. The authors investigated the cytoprotective effect of MCI-86 in a reperfusion model of myocardial ischemia. Rats were subjected to occlusion of the left coronary artery for ten minutes followed by reperfusion for twenty-four hours. The loss of myocardial creatine kinase activity (CK) from the left ventricular free wall (LVFW) twenty-four hours after the induction of myocardial ischemia was used as an index of ischemic damage. Administration of MCI-186 (3 mg/kg IV) significantly blunted the depletion of LVFW-CK activity when compared with vehicle (MCI-186 vs vehicle, 31.5 ± 1.1 vs 26.5 ± 1.2 U/mg protein, respectively,p<0.01). In another group of rats that underwent coronary artery occlusion—reperfusion, infarct size was measured by planimetry on histologic sections of serial slices of the left ventricle and was found to be 20.0 ± 1.3% of the left ventricle in vehicle-treated rats and 10.7 ± 1.3% in MCI-186 (3 mg/kg)-treated rats (p<0.01). These results indicate the potential usefulness of MCI-186 in myocardial ischemia-reperfusion injury.

Plasma levels of atrial natriuretic peptide in patients with Duchenne's progressive muscular dystrophy

To study the relationship between plasma alpha-atrial natriuretic peptide (alpha-ANP) and cardiac function in patients with Duchennes progressive muscular dystrophy (DMD), we measured plasma alpha-ANP levels in 51 patients with DMD and evaluated them according to the clinical severity of the disease and the echocardiographic left ventricular function. In many of the patients with DMD, plasma alpha-ANP levels were mildly elevated, but no clear correlation was observed between alpha-ANP levels and wall motion abnormalities of the left ventricle. The alpha-ANP level was moderately or markedly elevated (81 to 120 pg/ml) in 3 of the 16 patients with respiratory failure and extremely high (1208 pg/ml) in the one patient with congestive heart failure. Two patients with respiratory failure and one with congestive heart failure, in whom alpha-ANP levels were elevated, died within 2 months. Elevation of left atrial pressure as a result of left ventricular dysfunction caused by impairment of the myocardium and elevation of right atrial pressure as a result of pulmonary hypertension caused by impairment of the respiratory muscles are considered to be involved in the mechanism of increased plasma alpha-ANP levels in patients with DMD. It can be concluded that a moderate or marked elevation in plasma alpha-ANP levels in patients with terminal DMD is a sign of a poor prognosis and may be a useful index for the management of the disease.

A 10-year follow-up study by orthogonal Frank lead ECG on patients with progressive muscular dystrophy of the Duchenne type

A 10-year follow-up study by orthogonal Frank lead electrocardiography was performed on 25 patients with progressive muscular dystrophy of the Duchenne type (DMD). With advancing age, no apparent changes were observed in the duration and amplitude of the P wave or in the PR interval, whereas the duration of the QRS complex tended to increase. The amplitudes of the R wave in lead X (Rx) and lead Y (Ry) tended to decrease from 1.75 +/- 0.90 and 1.96 +/- 0.59 mV to 0.80 +/- 0.63 and 1.39 +/- 0.62 mV (p < 0.01), whereas the amplitude of the S wave in lead X tended to increase from 0.24 +/- 0.23 mV to 0.53 +/- 0.36 mV in 10 years after initiation of the study (p < 0.01). It is noteworthy that the Ry amplitude began to decrease markedly from the seventh year after the initiation of this study, whereas the Rx amplitude showed a gradual and unceasing decline through the 10-year period. Observation of the sequential changes of the QRS loops in three planes clearly demonstrated that the electrical force tended to decrease in the leftward and inferior directions and increase in the rightward direction. It is of interest that the frequency of occurrence of the deep Q wave was found to be quite high even in the early stages of DMD and that it did not display a direct relation to the sequential evolution of this disease. It can be concluded that observation of the sequential changes in the QRS complex allows estimation of the extent and direction of myocardial involvement in DMD.