Sadanori Ohtsuka

Coronary circulation in dogs with an experimental decrease in aortic compliance

OBJECTIVES This study was designed to investigate the effects of decreased aortic compliance on the coronary circulation. BACKGROUND A decrease in aortic compliance due to arteriosclerosis is observed in patients with coronary artery disease. However, the effects of decreased aortic compliance on the coronary circulation have not yet been investigated sufficiently. METHODS Hemodynamics, subendocardial electrocardiogram (ECG), myocardial segmental length and myocardial blood flow were investigated in six dogs with aortic bandaging (bandaged group) and five dogs with a sham operation (control group) at rest and during pacing 4 weeks after surgery. RESULTS Aortic compliance in the bandaged group was less than that in the control group (0.24 +/- 0.20 vs. 0.50 +/- 0.22 ml/mm Hg, p < 0.05). Pulse pressure and the tension-time index were significantly greater in the bandaged group than in the control group, but systemic vascular resistance was not altered significantly. The subendocardial/subepicardial flow ratio was lower in the bandaged group than in the control group (0.95 +/- 0.31 vs. 1.57 +/- 0.26, p < 0.05). In the region supplied by the left circumflex artery with a stenosis that was adjusted to eliminate reactive hyperemia, rapid atrial pacing (heart rate 200 beats/min) further decreased endocardial flow and the endocardial/epicardial flow ratio in the bandaged group. Moreover, both the reduction of segmental shortening and the ST elevation on the subendocardial ECG in the left circumflex-supplied region during pacing were greater in the bandaged group. CONCLUSIONS These results indicate that decreased aortic compliance greatly increases the risk of subendocardial ischemia in the presence of coronary stenosis.

Chronically decreased aortic distensibility causes deterioration of coronary perfusion during increased left ventricular contraction

OBJECTIVES This study investigated the long-term effects of decreased aortic distensibility on the heart in relation to coronary perfusion. BACKGROUND Aortic distensibility is decreased in patients with atherosclerosis and hypertension and in the elderly. However, the effect of a long-term decrease in aortic distensibility on coronary perfusion has not been fully investigated. METHODS Twelve anesthetized dogs underwent thoracotomy and were allocated to two groups: Group I included six control dogs with a normal aorta; Group II included six dogs with decreased aortic distensibility produced by banding the descending aorta. After 4 to 6 weeks, the dogs had a second operation to measure coronary artery flow and transmural flow distribution. Because the effect of decreased aortic distensibility on coronary perfusion may be affected by ventricular contractility, measurements were performed at baseline and during increased ventricular contraction induced by isoproterenol infusion. RESULTS At baseline, arterial compliance was reduced by 35% in Group II, but there was no change in total mean arterial resistance. Hemodynamic variables, regional wall motion and coronary flow were also similar in both groups. However, during isoproterenol infusion, coronary flow increased more in Group II than in Group I (p < 0.01), and the coronary flow reserve ratio (maximal peak hyperemic flow divided by rest flow) decreased more in Group II than in Group I (mean [+/- SD] 1.9 +/- 0.4 vs. 2.4 +/- 0.3, p < 0.05). Moreover, although the transmural flow distribution was similar in the two groups at baseline, during isoproterenol infusion the endocardial flow increased less in Group II than in Group I (p < 0.05), and the endocardial/epicardial flow ratio was significantly decreased in Group II compared with Group I (mean [+/- SD] 0.70 +/- 0.18 vs. 0.99 +/- 0.22, p < 0.05). The subendocardial electrocardiogram showed ST segment elevation during isoproterenol infusion in Group II (p < 0.05) but not in Group I. CONCLUSIONS These results demonstrate that during increased ventricular contraction, chronically decreased aortic distensibility contributes to a further decrease in the coronary flow reserve ratio, impairs endocardial blood flow and may induce subendocardial ischemia even in the absence of coronary artery stenosis.

Randomized, double-blind, placebo-controlled study of supplemental vitamin E on attenuation of the development of nitrate tolerance

The attenuation of intracellular production of cyclic guanosine monophosphate (cGMP) has been known as a mechanism of nitrate tolerance. A recent in vitro study have shown an increase in superoxide levels and a reduced activation of guanylate cyclase in tolerant vessels. We investigated the preventive effect of an antioxidant, vitamin E, on the development of nitrate tolerance. In this double-blind, placebo-controlled study, 24 normal volunteers and 24 patients with ischemic heart disease (IHD patients) were randomized to receive either vitamin E (200 mg t. i. d.; vitamin E group) or placebo (placebo group). Vasodilator response to nitroglycerin was assessed with forearm plethysmography by measuring the change in the forearm blood flow before and 5 min after sublingual administration of 0.3 mg nitroglycerin, and at the same time, blood samples were taken from veins to measure the platelet cGMP level. Measurements of the forearm blood flow and blood sampling were obtained serially at baseline (day 0), 3 days after taking vitamin E or placebo alone (day 3), and 3 days after application of a 10 mg/24 hr nitroglycerin tape concomitantly with oral vitamin E or placebo (day 6). The response of forearm blood flow (%FBF) and cGMP (%cGMP) after sublingual nitroglycerin on day 0(%FBF: normal volunteers 32 +/- 12% vs 31 +/- 11%, IHD patients 35 +/- 15% vs 34 +/- 15%; %cGMP: normal volunteers 38 +/- 10% vs 35 +/- 11%, IHD patients 37 +/- 11% vs 38 +/- 12%; vitamin E group as placebo group) and day 3(%FBF: normal volunteers 33 +/- 9% vs 32 +/- 12%, IHD patients 35 +/- 12% vs 33 +/- 13%, %cGMP: normal volunteers 38 +/- 10% vs 37 +/- 11%, IHD patients 36 +/- 14% vs 37 +/- 10%, vitamin E group vs placebo group) were not different between the two groups. On day 6 %FBF and %cGMP in the placebo group were significantly lower compared with day 0, and there were significant differences in them between the two groups (%FBF: normal volunteers 30 +/- 12% vs 17 +/- 9%, p < 0.01; IHD patients 28 +/- 14% vs 17 +/- 8%, p < 0.01; %cGMP: normal volunteers 35 +/- 11% vs 8 +/- 5%, p < 0.01; IHD patients 38 +/- 10% vs 12 +/- 4%, p < 0.01, vitamin E group vs placebo group). In conclusion, the combination therapy with vitamin E is potentially a useful method to prevent the development of nitrate tolerance.

Development of a two-dimensional imaging system for clinical applications of intravenous coronary angiography using intense synchrotron radiation produced by a multipole wiggler.

A two-dimensional clinical intravenous coronary angiography system, comprising a large-size view area produced by asymmetrical reflection from a silicon crystal using intense synchrotron radiation from a multipole wiggler and a two-dimensional detector with an image intensifier, has been completed. An advantage of the imaging system is that two-dimensional dynamic imaging of the cardiovascular system can be achieved due to its two-dimensional radiation field. This world-first two-dimensional system has been successfully adapted to clinical applications. Details of the imaging system are described in this paper.

Randomized, Double-Blind, Placebo-Controlled Study of Ascorbate on the Preventive Effect of Nitrate Tolerance in Patients With Congestive Heart Failure

BACKGROUND Reduced cGMP production caused by increased superoxide has been proposed as a mechanism of nitrate tolerance during continuous nitrate therapy. This study was designed to evaluate the effects of ascorbate, an antioxidant, on the development of nitrate tolerance during continuous nitrate therapy in patients with congestive heart failure. METHODS AND RESULTS Twenty patients with congestive heart failure were randomized to receive intravenous infusion of nitroglycerin concomitantly with placebo (placebo group, n=10) or intravenous ascorbate (vitamin C group, n=10). After baseline measurements were obtained, dose titration was started by the infusion of nitroglycerin at a rate of 0.5 microg/kg per minute (titration period). Measurements of hemodynamic parameters and blood sampling were performed serially at 0, 6, 12, 18, and 24 hours after the titration period. At baseline, mean pulmonary artery pressure (MPAP, mm Hg), mean pulmonary capillary wedge pressure (PCWP, mm Hg), plasma vitamin E level (micromol/L), and platelet cGMP level (pmol/10[9] platelets) were comparable in the two groups (placebo group: MPAP, 48+/-6; PCWP, 24+/-4; cGMP, 0.76+/-0.12; vitamin E, 18.2+/-1.2; vitamin C: MPAP, 49+/-7; PCWP, 24+/-4; cGMP, 0.71+/-0.16; vitamin E, 18.6+/-1.3). In both groups, at 6 hours after the titration period, MPAP and PCWP were significantly decreased (placebo group: MPAP, 26+/-5; PCWP, 15+/-4; vitamin C: MPAP, 26+/-4; PCWP, 16+/-4), and platelet cGMP was significantly increased (placebo group: 2.42+/-0.24; vitamin C: 2.26+/-0.26). However, at 18 hours after titration, in the placebo group, MPAP (44+/-5) and PCWP (23+/-4) were increased, and platelet cGMP (0.85+/-0.20) and plasma vitamin E levels (12.4+/-1.4) were significantly decreased. In contrast, in the vitamin C group, MPAP (31+/-6), PCWP (17+/-5), platelet cGMP (2.49+/-0.23), and plasma vitamin E levels (17.6+/-1.4) were maintained for 18 hours after the titration period. CONCLUSIONS These findings indicate that ascorbate, an antioxidant, may prevent the development of nitrate tolerance during continuous nitrate therapy in patients with congestive heart failure.

Platelet cyclic GMP. A potentially useful indicator to evaluate the effects of nitroglycerin and nitrate tolerance.

BackgroundThe present study was designed to investigate the intracellular production of cyclic GMP (cGMP) in platelets in response to nitroglycerin and to determine the potential clinical value of platelet cGMP as an indicator of the effects of nitroglycerin and nitrate tolerance. Methods and ResultsPlatelet cGMP levels and the diameters of the coronary arteries before and 2 minutes after intracoronary injection of 200 ptg nitroglycerin were measured in 15 patients who had previously received nitrates (nitrates group) and in 16 who had not received any nitrates (no-nitrates group). Platelet cGMP levels increased significantly after nitroglycerin injection in the two groups, but plasma cGMP levels and plasma atrial natriuretic peptide levels did not change. The percent increase in platelet cGMP levels and the percent dilatation of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries after nitroglycerin injection were higher in the no-nitrates group than in the nitrates group (platelet cGMP levels: artery, 74.2±18.3% versus 11.5

Randomized, double-blind, placebo-controlled study of the preventive effect of supplemental oral vitamin C on attenuation of development of nitrate tolerance.

4.2%, p<.01; vein, 73.6+22.9%o versus 9.0

Alterations in left ventricular wall stress and coronary circulation in patients with isolated systolic hypertension.

3.1%, p<.01; coronary dilatation: LAD, 46.7

Two-dimensional intravenous coronary arteriography using above-K-edge monochromatic synchrotron x-ray

6.0%o versus 9.9

Amlodipine improves vascular function in patients with moderate to severe hypertension.

2.5%, p<.01, LCx, 51.2+8.7% versus 6.1