Tamotsu Takita

Nitric oxide modulates sympathetic control of left ventricular contraction in vivo in the dog

Recently, evidence has been presented that nitric oxide (NO) modulates myocardial contraction induced by beta-adrenergic stimulation in vitro and in vivo. In this study, we investigated whether inhibition of the L-arginine NO system augments the positive inotropic response of the left ventricle to direct stimulation of the sympathetic nerves in vivo in the dog. Electrical stimulation was applied to the left stellate ganglion (LSG) for 1 min at submaximal (5 V, 2.5, 5 and 10 Hz) and supramaximal intensities (10 V, 10 Hz) in twelve anesthetized and vagotomized dogs. Next, in the same dogs, N(omega)-nitro L-arginine methylester (L-NAME) was infused into the left anterior descending (LAD) coronary artery, and LSG stimulation repeated using the same protocol. Finally, L-arginine was infused into the LAD artery, and LSG stimulation repeated. We used the maximum of the first derivative of left ventricular pressure (LV max d P/dt) as an index of the myocardial contractility. Plasma epinephrine and norepinephrine concentrations were measured in the coronary sinus at 5 V, 2.5 Hz before and after L-NAME treatment in five of twelve dogs. L-NAME treatment significantly augmented the inotropic response of the left ventricle (percent change in the LV max dP/dt) to LSG submaximal stimulation trains from 164 +/- 13 to.212 +/- 21 (P < 0.03), from 187 +/- 15 to 234 +/- 25 (P < 0.05) and from 220 +/- 19 to 280 +/- 33% (P < 0.05), respectively. This response was reversed by L-arginine treatment. However, the inotropic response to the supramaximal stimulation train did not change after L-NAME and L-arginine treatment. L-NAME significantly increased plasma norepinephrine concentration from 0.69 +/- 0.41 to 1.00 +/- 0.52 ng/ml without changing plasma epinephrine concentration in the coronary sinus. It is concluded that the inhibition of the L-arginine NO system augmented the positive inotropic effect on the left ventricle during sympathetic nerve stimulation in normal dogs in vivo.

Non-invasive estimation of human left ventricular end-diastolic pressure

Sato et al. (Electronic Letters 32, 949-950, 1996) reported that one can obtain a non-invasive estimate of left ventricular (LV) pressure at around end-diastole in an isolated canine preparation. In this study we examined whether this method can be applied to humans. Using the method proposed by Kanai et al. (IEEE. Trans. UFFC, 43, 791-810,1996), we detected small amplitude LV vibration from an ultrasonic pulse Doppler signal reflected from the interventricular septum in five patients (44-63 y.o., male;4, female;1). We measured the oscillation frequency of the LV wall through the wavelet transform of small amplitude LV vibration, and calculated LV pressure at around end-diastole from the values of oscillation frequency, internal radius and wall thickness using Mirskys equation. The estimated LV pressures at around end-diastole were similar to end-diastolic pressure measured directly by cardiac catheterization. These results show the possibility that this method allows for the non-invasive estimate of LV pressure at around end-diastole, and furthermore provides the basis for future clinical applicability of this technique.

Immunohistochemical Analysis of Platelet-derived Growth Factor-B Expression in Myocardial Tissues In Hypertrophic Cardiomyopathy

Intimal and/or medial hyperplasia of intramyocardial small vessels is thought to be one of the causes of myocardial ischemia in hypertrophic cardiomyopathy (HCM). However, the pathogenesis of such vascular lesions in HCM is not yet known. To evaluate the pathogenic role of platelet-derived growth factor (PDGF-B) and basic fibroblast growth factor (b-FGF), which have a potential to induce cellular and molecular changes observed in the vessels in HCM, we examined the expression of these molecules and PDGF receptors in cardiac tissues from six patients with HCM and seven controls using immunohistochemistry. The percentage of PDGF-B positive cells in the myocyte population in HCM was significantly higher than that in controls (52.6 +/- 16.2 (mean +/- SD) vs. 21.6 +/- 9.6, p < 0.01). PDGF-B was also observed in vascular regions in HCM (61.1 +/- 25.5% of arterioles) but not in controls. There were no significant differences in the expression of b-FGF and PDGF receptors in the myocyte and non-myocyte populations and the vascular regions between the HCM and control groups. Our study revealed that the expression of PDGF-B protein was up-regulated in HCM, suggesting the contribution of this molecule to the development of intramyocardial vasculopathy.

Effects of percutaneous transluminal mitral valvuloplasty on plasma catecholamine levels during exercise

Elevation of plasma catecholamine levels during exercise in patients with mitral stenosis correlated with the severity of the disease. We investigated the plasma norepinephrine changes in six patients before and after percutaneous transluminal mitral valvuloplasty (PTMV) during continuously graded ergometer exercise. Peak exercise intensity was increased from 65.8 W to 87.5 W after PTMV. Plasma norepinephrine level at 60 W workload intensity was decreased from 2308 +/- 864 pg/ml to 841 +/- 233 pg/ml after PTMV (p < 0.05). We concluded that PTMV decreased the plasma norepinephrine level during exercise in the patients with mitral stenosis. Percutaneous transluminal mitral valvuloplasty is a novel procedure for the improvement of symptoms in patients with mitral stenosis.