Minoru Mitsugi

Cilostazol, a novel cyclic AMP phosphodiesterase inhibitor, prevents reocclusion after coronary arterial thrombolysis with recombinant tissue-type plasminogen activator.

Inhibitors of cyclic nucleotide phosphodiesterase hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate are known to inhibit platelet aggregation, which plays an important role in acute reocclusion after thrombolysis in acute myocardial infarction. In the present study of a canine preparation of coronary artery thrombosis superimposed on high-grade stenosis, we tested whether the antithrombotic agent cilostazol, an inhibitor of cAMP phosphodiesterase, could prevent acute reocclusion or sustain coronary blood flow after thrombolysis when used with recombinant tissue-type plasminogen activator (rt-PA) and heparin. Intravenous infusion of rt-PA (0.5 mg/kg body wt for 30 minutes) and heparin (a 150 IU/kg body wt i.v. bolus and then 25 IU/kg body wt per hour i.v.) was combined with cilostazol (0.6 or 1.8 mg/kg body wt for 60 minutes). Without cilostazol, reperfusion was observed in seven of eight dogs, but reocclusion occurred in six of these seven dogs after 9 +/- 2 minutes. After administration of 1.8 mg/kg body wt cilostazol (group B-2; a 120-minute observation after the start of rt-PA infusion), reperfusion occurred in all seven dogs (p < 0.05 versus control group), and brief cyclic reocclusion was observed in only one dog 63 minutes after reperfusion. At the same dose of cilostazol (group B-2L; a 240-minute observation after the start of rt-PA infusion), reperfusion occurred in all five dogs (p < 0.05 versus control group), and coronary blood flow was well maintained except for one short reocclusion in one dog. Cilostazol inhibited cyclic flow reduction in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of synchronized retroperfusion on the coronary arterial pressure : flow relationship

OBJECTIVE We compared the effects of diastolic coronary sinus pressure elevation due to synchronized retroperfusion (SRP) with systolic coronary sinus pressure elevation due to coronary sinus occlusion on the coronary pressure-flow relationship under similar mean coronary sinus pressure values. METHODS Using isolated, perfused canine hearts, coronary perfusion of the left anterior descending artery was reduced gradually, setting the mean coronary sinus pressure to 14.2 +/- 5.7 mmHg (mean +/- s.d.) under control conditions, 30.3 +/- 4.9 mmHg under SRP with lower retrograde perfusion flow [SRP(L)], 30.7 +/- 4.6 mmHg under coronary sinus partial occlusion [CSPO], 51.9 +/- 7.9 mmHg under SRP with higher retrograde perfusion flow [SRP(H)] and 49.0 +/- 7.9 mmHg under coronary sinus complete occlusion [CSCO]. Zero-flow pressure and the slopes of pressure-flow relationship were determined in each condition. RESULTS The mean values of the slopes did not significantly differ among the interventions. The mean control value of zero-flow pressure was 17.4 +/- 4.3 mmHg. Zero-flow pressure of SRP(L) was 20.0 +/- 3.5 mmHg, which was not a significant increase, whilst zero-flow pressure of CSPO was 22.9 +/- 3.4 mmHg, a significant increase compared with control (P < 0.05). Zero-flow pressure of SRP(H) and CSCO was 26.0 +/- 4.5 and 31.3 +/- 6.7 mmHg, respectively, and both were significantly higher than control (P < 0.01). Zero-flow pressure of SRP(H) was, however, significantly lower than CSCO (P < 0.05). CONCLUSIONS SRP, which causes diastolic coronary sinus pressure elevation, does not greatly affect coronary arterial inflow, compared with coronary sinus occlusion which causes systolic coronary sinus pressure elevation. These results suggest that the blood volume contained in the heart during systole plays a role in determining coronary inflow. Therefore, SRP intervention, which does not interfere with venous outflow during systole, may ameliorate injured myocardium during ischaemia without seriously affecting coronary inflow supply.

Effects of Coronary Collateral Circulation and Outflow Pressure Elevation on Coronary Pressure-Flow Relationships in The Beating and Non-Beating States

Many factors are known to influence pressure intercept and curvilinearity of coronary pressure-flow (P-F) relationships. In this paper, we focused on two of them, interarterial collateral circulation and outflow pressure elevation. We reviewed previous reports and reexamined their effects from the viewpoint of the beating/non-beating state. The presence of interarterial perfusion pressure gradients between the left anterior descending artery and the remaining vessels resulted in an increase in zero flow pressure (Pf = 0) and a more linear slope of the P-F relationship to the same degree in both the beating and non-beating states, through interarterial collateral circulation. This indicates that collateral circulation is not necessarily inhibited by cardiac contraction. Coronary outflow pressure elevation due to coronary sinus occlusion caused an increase in Pf = 0 without altering the slope of the P-F relationship, and the slope in the non-beating state shifted to the right more than in the beating state when coronary sinus pressure was elevated to the same level of 30 mmHg.

Paget-Schroetter Syndrome in a Baseball Pitcher

Paget-Schroetter syndrome (PSS) is thrombosis of the deep veins draining the upper extremity due to anatomic abnormalities of the thoracic outlet that cause subclavian compression and subsequent thrombosis, leading to thrombus formation in the subclavian vein. Vigorous arm activity in sports is a known risk factor. Here, we report a case of Paget-Schroetter syndrome in a 31-year-old male non-professional baseball pitcher.

Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension.

Background Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP) control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) combination tablet containing a regular dose of irbesartan (100 mg) and a high dose of amlodipine (10 mg) with regard to lowering BP and other risk factors for cardiovascular disease. Methods We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB. Results The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol levels, independent of the BP-lowering effect. Treatment with the combination tablet did not affect serum triglycerides, plasma glucose, glycated hemoglobin, serum potassium or creatinine levels, or the urinary albumin excretion rate. Conclusion The combination tablet containing amlodipine 10 mg and irbesartan 100 mg had a greater BP-lowering effect than an ARB and a low-dose or regular-dose CCB. In addition, the combination tablet had more favorable effects on serum uric acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels in patients with hypertension.

Interaction Between Left-Ventricular Function and Loading Condition in Cardiovascular Disease

In this chapter, interactions between ventricular performance, loading condition, and coronary circulation are described from the standpoint of pathogenesis of the progression or amelioration of cardiac dysfunction. A decrease in peripheral resistance increases stroke volume until a certain critical level of afterload reduction; thus, afterload-reducing therapy is frequently performed in patients with heart failure. When afterload reducing is performed in cardiac dysfunction with regional ischemia, increased stroke volume is also found, as observed in global ischemia. However, the meaning of augmented ejected volume from the heart differs between regional and global ischemia. In regional ischemia, cardiac output continues to increase after progressive afterload reduction despite the appearance of functional aggravation in the ischemic region. Thus, the afterload, at which the maximal cardiac output is obtained, may not necessarily indicate optimal loading level in this type of cardiac dysfunction. This must be considered clinically when adopting afterload reducing therapy in regional ischemia. Moreover, when intraaortic balloon pumping (IABP) is used for patients with heart failure from coronary artery disease, the aortic pressure level of the pre-IABP stage must be also considered to attain suitable cardiac pump function. Decrease in arterial compliance leads to systolic hypertension and then finally to heart failure via increased ventricular afterload during systole. Conversely, in heart failure arterial compliance seems to decrease as a result of changes in vessel wall characteristics, and cardiac dysfunction might then further decline. When decreased arterial compliance is introduced to a depressed heart, ventricular ejection is impaired significantly, compared to the heart with normal contractility; moreover, the rate of decrease of stroke volume may be different, depending on the cause of cardiac dysfunction. An increase in diastolic filling pressure is frequently found in heart failure. Elevation of left-ventricular filling pressure increases zero-flow pressure of the left coronary pressure—flow relationship without showing significant change in the slope of the coronary pressure—flow relationship. The presence of the pericardium further increases the zero-flow pressure value of coronary pressure—flow relationship, which is obtained at the same filling pressure without the pericardium. In addition, increased filling pressure decreases diastolic compliance in both the related ventricle and the ventricle of the opposite side. Accordingly, when diastolic filling pressure increases, cardiac chamber interactions are found in chamber stiffness and also in the coronary pressure—flow relationship. As supportive therapy for myocardial ischemic injury and subsequent ischemia-induced cardiac dysfunction, synchronized retroperfusion is used as well as IABP. Synchronized retroperfusion delivers arterial blood flow during diastole and increases downstream venous pressure in the pathway of the coronary sinus; this reduces coronary driving pressure in diastole, and the coronary pressure—flow relationship is significantly shifted to the right. However, impairment of coronary pressure—flow relationship following diastolic downstream pressure elevation is much less than that in the systolic change when compared at the same mean downstream pressure elevation, indicating that the phase of downstream pressure elevation is also important in coronary inflow mechanics. From the same experimental series, it becomes apparent that coronary sinus pressure elevation via synchronized retroperfusion promotes collateral flow to the ischemic region, when concomitant with cardiac contraction. Finally there are many unclear but important interactions including these issues. These interactions play an important role in regulating cardiac function, especially in disease, and such information is therefore necessary for understanding pathophysiology or performing treatment in cardiovascular diseases.