Shigetake Sasayama

Heart Disease in Asia

People desirous of knowing the diversities of the races of mankind, as well as the diversities of regions of all parts of the East, read through this book and you will find in it the greatest and most marvelous characteristics of the people … From the Prologue to The Travels of Marco Polo With the advent of an aging society, heart disease has become one of the most important health problems worldwide. Heart disease is estimated to increase continuously during the next few decades. In fact, the number of people ≥60 years of age is expected to double by 2025 and to triple by 2050 globally.1 The proportion of this aged population is likely to increase more in the Asian-Pacific region; thus, half of the world’s cardiovascular burden is predicted to occur in this area.2 Increases in levels of risk factors, in particular total cholesterol and blood pressure, appear to account for a substantial amount of the age-related increase in coronary heart disease. This themed issue highlights the perspective for the contributions of risk factors to the excess coronary heart disease mortality in populations of the Asia-Pacific region. Cardiovascular risk factors are traditionally derived from studies in whites. However, relationships between these traditional risk factors and cardiovascular disease may differ in Asian and Western societies. The ethnic differences in the association between diabetes mellitus and ischemic heart disease are noted even within Asian populations.3 In Asian countries, as a consequence of the economic developments, the prevalence of overweight and obesity is increasing, and more important, rates of diabetes are increasing even more quickly. In particular, a moderate increase in body mass index makes South Asians more prone to insulin resistance and related diseases.4 Thus, it has been suggested that lower cutoff points for body mass index …

Disparate inotropic and lusitropic responses to pimobendan in conscious dogs with tachycardia-induced heart failure.

Left ventricular (LV) inotropic and lusitropic responses to a calcium sensitizer, pimobendan, were compared between normal and failing hearts. Heart failure was induced by rapid ventricular pacing in 6 dogs instrumented with a micromanometer and a conductance catheter. The effects of pimobendan were evaluated in the conscious state before and after development of heart failure. Pimobendan dose-dependently increased the slope of the end-systolic pressure-volume (P-V) relation (Ees) in both normal and failing hearts, whereas its magnitude was markedly attenuated in failing hearts. Heart rate (HR) was increased by pimobendan in normal heart but did not change in failing heart. LV relaxation, assessed by peak - dP/dt and the time constant of isovolumic pressure decay (Td), was substantially improved to the same extent in failing and normal hearts. Consequently, Ees and Td exhibited a hyperbolic relation over a wide range of contractility states. In normal heart, pimobendan caused a leftward shift of the diastolic P-V relation while maintaining a similar curve. In failing heart, however, this relation shifted directly downward with a concomitant increase in end-diastolic volume, indicating a reduction in the constraints on LV distention and a resultant increase in preload reserve. Thus, pimobendan accelerated LV isovolumic relaxation and improved distensibility in conscious dogs with tachycardia-induced heart failure despite the marked attenuation of inotropic responses.

Diastolic Dysfunction in Experimental Heart Failure

The most common hemodynamic abnormality seen in patients with heart failure is an elevation in left ventricular filling pressure. This elevation may be related to an increase in left ventricular diastolic volume as a consequence of depressed contractile performance or an alteration in the diastolic properties with a direct shift of the diastolic pressure-volume relation and impaired ventricular relaxation. Both may also play a role simultaneously in causing the increased filling pressure. Diastolic dysfunction may precede impairment of systolic function or could be mediated directly by depressed systolic shortening [1]. Disparity between recovery of systolic and diastolic function during regression of supraventricular tachycardia-induced cardiomyopathy has also been noted [2].

Reappraisal of Functional Importance of Coronary Collateral Circulation

Coronary collateral circulation (CCC) is defined as an alternative blood-conveying circuit to the ischemic myocardium supplied by a jeopardized coronary artery. Accumulating evidence on CCC and its functional role has been derived from basic and clinical studies over several decades. Progress in molecular biology and genetic engineering has enabled us to elucidate the mechanisms of collateral growth on the basis of the development of new experimental models and methods for accurate assessment of CCC. These achievements in basic research have been promptly translated into the clinical setting. Interaction between basic and clinical sciences in the fascinating field of CCC will contribute to the establishment of innovative collateral-promoting therapy for severe coronary artery disease.

Treatment options for Cheyne-Stokes respiration and heart failure.

A national survey in Japan has revealed that about one of five adults in the general population suffers from a sleep problem [1]. However, sleep-disordered breathing (SDB) had not been well recognized as a substantial health issue in Japan until March of 2003, when a bullet-train driver fell asleep for 8 min while the train was running and an automatic safety system stopped the train while it was traveling at 270 km/h. A few days after this event, the 33-year-old driver was diagnosed as having serious sleep apnea. The Science Council of Japan now has started a national project to promote research, education, technology transfer, and coordination, similar to the Coalition to Wake Up America in the United States. As a matter of course, the awareness of SDB has increased to a significant extent. Nowadays, many people live to an advanced age in Japan, and with the advent of the aging society, congestive heart failure (CHF) has become one of the most important health problems, constituting a major cause of death in elderly patients. Despite development of a number of innovative pharmacological therapies, morbidity and mortality rates of CHF remain still high. Therefore, there have been substantial efforts to determine all treatable conditions that exacerbate CHF. There now is convincing evidence that mortality increases in CHF patients with SDB compared with those without, irrespective of degree of left ventricular (LV) dysfunction. Nevertheless, only limited attention has been paid to SDB as a potential therapeutic target until quite recently. There are two forms of SDB, obstructive sleep apnea (OSA) and central sleep apnea (CSA). Although CSA is relatively rare in the general population, prospective studies revealed that 33% to 82% of patients with CHF have evidence of CSA and characteristic Cheyne-Stokes respiration (CSR).

Effects of diltiazem and verapamil on (+)PN200-110 binding kinetics in dog cardiac membranes

The effects of d-cis-diltiazem (diltiazem) and verapamil on 1,4-dihydropyridine binding to dog cardiac membranes were studied in competition, saturation and kinetic binding experiments with [3H](+)-PN200-110. Diltiazem increased [3H](+)-PN200-110 binding with an observed maximal effect at 50 microM, while verapamil decreased [3H](+)-PN200-110 binding in a dose-dependent manner. Scatchard analysis of saturation binding data revealed that diltiazem (50 microM) increased the maximal binding site density and verapamil (100 microM) increased the dissociation constant (KD) of [3H](+)-PN200-110 binding. The kinetic experiments demonstrated that diltiazem significantly reduced both the association and the dissociation rate of [3H](+)-PN200-110 binding, resulting in no significant change in the apparent KD. In contrast, verapamil accelerated dissociation and slowed down association of [3H](+)-PN200-110 binding. Diltiazem appears to alter both the number of [3H](+)-PN200-110 binding sites and the characteristics of [3H](+)-PN200-110 binding.