Hiroyuki Shimamoto

Lisinopril Improves Aortic Compliance and Renal Flow: Comparison With Nifedipine

We compared the systemic and regional hemodynamic effects of nifedipine and lisinopril in 26 elderly hypertensive patients with the use of the pulsed Doppler ultrasound technique. Nifedipine is a dihydropyridine calcium antagonist, and lisinopril is an angiotensin-converting enzyme inhibitor. The study had a single-blind crossover design: nifedipine and lisinopril were given for 8 weeks each after washout periods of 4 weeks. Both nifedipine and lisinopril significantly reduced mean arterial pressure to the same extent (P < .01); cardiac output remained unchanged in both nifedipine- and lisinopril-treated groups. Lisinopril increased renal flow significantly (P < .01), but nifedipine did not. Common carotid, vertebral, celiac, and superior mesenteric arterial and diaphragmatic and terminal aortic flows did not show a significant change with either nifedipine or lisinopril. The specific action of lisinopril on the thoracic aorta was a marked improvement of aortic compliance compared with nifedipine, which might be partly responsible for an increase in renal flow. Lisinopril may provide more desirable regional hemodynamic effects and additional benefits for elderly hypertensive patients.

Lisinopril Reverses Left Ventricular Hypertrophy Through Improved Aortic Compliance

We treated with nifedipine or lisinopril 38 essential hypertensive patients with left ventricular hypertrophy. The study had a single-blind crossover design; nifedipine or lisinopril was given for the first 24 weeks, and then patients were crossed over to the other antihypertensive agent for another 24 weeks. Both nifedipine and lisinopril significantly decreased mean arterial pressure to the same extent. Although lisinopril decreased left ventricular mass index more rapidly than nifedipine, 48 weeks of antihypertensive treatment with nifedipine or lisinopril reduced the extent of left ventricular hypertrophy to the same level. Stepwise multiple linear regression analysis revealed that the reversal of left ventricular hypertrophy may be mainly due to a reduction in mean arterial pressure during the 24-week nifedipine treatment and due to an improvement of aortic compliance during the lisinopril treatment. Both nifedipine and lisinopril are effective in the reversal of hypertensive left ventricular hypertrophy; however, the agents have disparate actions on hemodynamic factors.

Transoesophageal Doppler echocardiographic measurement of cardiac output by the mitral annulus method

Objective—To compare cardiac output measured by the transoesophageal Doppler and thermodilution techniques. Design—Prospective direct comparison of paired measurements by both techniques in each patient. Setting—Intensive care unit in a cardiovascular centre. Patients—65 patients after open heart surgery (mean (SD) age 53 (12) years). Interventions—Cardiac output was measured simultaneously by the transoesophageal Doppler and thermodilution techniques. Cardiac output was measured again after a mechanical intervention or volume loading. Results—The limits of agreement were −2·53 to +0·83 1·min−1 for cardiac output measured by the Doppler and thermodilution techniques. This suggests that the Doppler method alone would not be suitable for clinical use. The second measurement of cardiac output by thermodilution was compared with cardiac output estimated from the first and second Doppler measurements and the first thermodilution measurement. The limits of agreement (−0·55 to +0·51 1·min−1) were good enough for clinical use. Conclusions—After cardiac output had been measured simultaneously by both the Doppler and thermodilution techniques, subsequent transoesophageal Doppler alone gave a clinically useful measurement of cardiac output.

Time course of hemodynamic responses to sodium in elderly hypertensive patients.

Thirty-one patients with essential hypertension (81.6 +/- 6.9 years old) were studied during two different regimens of sodium intake: 120 meq/day for 8 weeks and 344 meq/day for 2 weeks. Systemic hemodynamic data were measured with Doppler echocardiography from which the mitral flow velocity integral, cardiac index, and total peripheral resistance were calculated. The salt-sensitive patients in whom the increase in total peripheral resistance was greater than the increase in cardiac index with salt loading were termed SST. In the salt-sensitive patients termed SSC, the increase in cardiac index was greater than the increase in total peripheral resistance with increased sodium intake. All SST patients on day 7 of the high sodium diet remained in the SST group on day 14. Nine of 13 patients in the SSC group on day 7 remained in the SSC group on day 14, and the remaining four patients in the SSC group on day 7 fell into the SST group on day 14. Four of eight non-salt-sensitive (NSS) patients on day 7 of the high salt regimen remained in the NSS group on day 14, whereas the remaining four patients in the NSS group on day 7 fell into the SSC group on day 14. Our data suggest a changing pattern with sodium loading of initially high cardiac index followed by a persistently raised total peripheral resistance. The celiac, superior mesenteric, and renal arteries vasoconstricted with sodium repletion in both SST and SSC patients. With salt loading, the terminal aortic vascular bed vasodilated in the SSC patients and vasoconstricted in the SST patients.

Activation of protein kinase C as a modulator of potentiated UK-14304-induced contractions in dog mesenteric artery and vein

We assessed the role of protein kinase C (PKC) in the mechanism responsible for the potentiation of UK-14304-induced contractions produced when isolated dog mesenteric vascular rings were pretreated with threshold concentrations of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), KCl, or endothelin-1 (ET-1). In dog mesenteric artery. UK-14304 produced a biphasic concentration-response curve in the presence of TPA, KCl, or ET-1, with the curve portion at lower concentrations being alpha 2-adrenoceptor dependent and the portion at higher concentrations being alpha 1-adrenoceptor dependent. Calphostin C (10(-6)M), a PKC inhibitor, abolished amplified UK-14304-induced contraction in the TPA-pretreated tissues. In the KCl- and ET-1-pretreated tissues. 10(-6)M calphostin C antagonized amplified UK-14304-induced contractions by approximately 20% in both parts of the concentration-response curve. In contrast, in dog mesenteric vein, amplified UK-14304-induced contractions by TPA, KCl, and ET-1 were entirely dependent on alpha 2-adrenoceptors. Calphostin C (10(-6)M), which in control experiments had no effect on KCl-induced contraction and antagonized responses to TPA by 60.1%, inhibited UK-14304-induced contraction by 18.3%. Amplified UK-14304-induced contraction was antagonized by 10(-6)M calphostin C by 21.8% in KCl-precontracted tissues, 58.1% in ET-1-precontracted tissues, and 66.3% in TPA-precontracted tissues. In the ET-1- and TPA-pretreated dog mesenteric veins, 10(-6)M calphostin C decreased maximal tensions of enhanced UK-14304-induced contractions to the same level as the UK-14304-induced maximal tension inhibited by 10(-6)M calphostin C in untreated dog mesenteric vein. Therefore, TPA can be a precontracting agent that amplifies UK-14304-induced contractions through PKC activation in both dog mesenteric artery and vein. PKC predominantly mediates the contraction amplification mechanisms after exposure to ET-1 in dog mesenteric vein and does not play a major role in the amplification of UK-14304-induced contraction by KCl in both dog mesenteric artery and vein. These data show that a common mechanism need not underlie amplification of adrenergic responses in mesenteric artery and vein.

Quantitative Pulsed Doppler Measurement of Arterial Blood Flows in Humans

Doppler flowmetry was assessed in 11 adult patients whose admission diag noses included aneurysm of the aorta or dissections. During surgery, regional blood flows of the left common carotid artery, terminal aorta, common iliac artery, external iliac artery, or common femoral artery were measured by Dop pler method and electromagnetic flowmeter. Eighty-four arterial flow determi nation were obtained from the 11 patients studied. On comparison of simultaneous electromagnetic and Doppler measurements of blood flow, an ex cellent correlation (r=0.93) was found between the two methods. The slope of the regression line was about 0.587. Regional blood flows were measured with Doppler flowmetry in another 11 patients. The values of the left common carotid, celiac, superior mesenteric, and terminal aortic flows were 255 ± 59, 618 ± 384, 670 ± 380, and 810 ± 325 mL/min, respectively. This method seems to be valua ble clinically in quantitative measurements of arterial flows in humans.

Effects of intraaortic balloon pumping on mitral flow dynamics in patients with coronary artery bypass operations

We evaluated the improvement in left ventricular function in 26 patients after coronary artery bypass grafting who were treated with intraaortic balloon pumping (IABP). Mitral flow velocity-time integral in the rapid filling phase (IntR) and that in the atrial contraction phase (IntA), the sum of IntR and IntA (IntR+IntA), and the ratio of IntA to IntR (IntA/IntR) were calculated with patients on and off balloon pumping (IABP ON-OFF test). IABP increased IntR and IntR+IntA, decreased IntA/IntR, and did not change IntA, suggesting that a decreased afterload or augmented coronary perfusion improves left ventricular relaxation. When the balloon inflated on every other beat (IABP 1:2 test), IntR and IntR+IntA increased without balloon assist, IntA/IntR decreased off IABP, and IntA did not change. The afterload reduction or augmented coronary perfusion on the previous beat with IABP might help ventricular filling on the next beat without balloon assist. A drastic decrease in IntR after IABP stopped indicated the need to continue IABP. Since the change in IntR during IABP ON-OFF test was significantly correlated with that in IntR during IABP 1:2 test, the change in IntR during IABP 1:2 test could help to predict the optimal time of weaning.

The influence of thyroid function on the circadian rhythm of heart rate in elderly euthyroid subjects

The influence of thyroid function on the circadian rhythm of heart rate was assessed using 24 hour electrocardiographic recordings in 196 elderly euthyroid subjects (78.4 +/- 8.1 years; male 60, 76.1 +/- 9.1 years; female 136, 79.4 +/- 7.4 years). Serum free T3, free T4 and TSH levels were measured by radioimmunoassay. To determine if heart rate fluctuates rhythmically with a circadian period, mean hourly heart rates in 24 hour electrocardiographic recordings were used to fit cosine curves by the statistical technique of least squares, and the parameters of the rhythm--the mesor, amplitude, acrophase, maximal and minimal hourly heart rates--were estimated. To investigate the factors influencing the diurnal variation of heart rate, we applied multiple regression analysis. The cosine curves were fitted with a P value of 0.01 or less in all subjects. The mesor, maximal and minimal hourly heart rates were inversely proportional to serum TSH concentrations in males. Neither amplitude nor acrophase had relation to the thyroid function in males. The mesor, maximal and minimal hourly heart rates were directly proportional to serum-free T4 concentrations and inversely proportional to serum TSH concentrations in females. The increase in the acrophase correlated with the increase in serum-free T4 levels, and the acrophase increased in proportion to serum-free T3 levels in females.

高齢者内科的消耗性疾患における Total Parenteral Nutrition による心拍数概日リズムへの影響

The circadian rhythm of the heart rate was assessed using 24 hour electrocardiographic recordings in 18 hospitalized elderly patients with wasting diseases receiving total parenteral nutrition. The nutrient solutions were administered at doses ranging from 360 to 1640 kcal/day. To determine if the heart rate fluctuates rhythmically with a circadian period, the mean hourly heart rate on 24 hour electrocardiographic recordings was used to fit cosine curves by the statistical technique of least squares, and three parameters of the rhythm--designated the mesor, amplitude, and acrophase--were estimated. The cosine curves fitted with a P value of 0.01 or less in all patients before and after insertion of central venous catheters. The mesor represented the rhythm--adjusted mean of the heart rate. The mesor increased significantly with increase in the energy infusion rate (p less than 0.01). The amplitude values were derived from one half of the total diurnal variation of heart rate and the acrophase indicated the time when heart rates were at their peak above the mean. Neither amplitude nor acrophase changed significantly with increase in the energy infusion rate. Furthermore, neither norepinephrine nor epinephrine plasma levels changed with nutrient administration. There were no significant changes in thyroid hormone concentrations. There was a significant positive correlation between mesor changes and rectal temperature with increase in the energy infusion rate (r = 0.76, p less than 0.01). In severely malnourished subjects, changes in the level of feeding can profoundly affect cardiac functions and thermogenic response.