Narihisa Matsuyama

Sympathetic Nervous Activity and Myocardial Damage Immediately After Subarachnoid Hemorrhage in a Unique Animal Model

Background and Purpose— Obvious cardiac dysfunction, including ECG abnormalities and left ventricular asynergy, is known to develop after subarachnoid hemorrhage (SAH). To clarify the close relationship between myocardial damage and sympathetic nervous activity immediately after SAH, a novel experimental animal model was used. Methods— SAH was provoked by perforation of the basilar artery with the use of a microcatheter inserted through the femoral artery in 18 beagle dogs. Hemodynamic changes were recorded, and plasma concentrations of noradrenaline, adrenaline, and 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG) and serum levels of creatine kinase–MB (CK-MB) and troponin T were measured at 0, 5, 15, 30, 60, 120, and 180 minutes after SAH. Results— Noradrenaline (pg/mL), adrenaline (pg/mL), and MHPG (ng/mL) increased abruptly from 120±70, 130±70, and 1.3±0.5 before SAH to 1700±1200, 5600±3500, and 3.2±1.2 at 5 minutes after SAH, respectively. Aortic pressure, left ventricular wall motion, and cardiac output increased by 60%, 40%, and 30%, respectively (P <0.001) at 5 minutes and then decreased by 50%, 55%, and 40%, respectively (P <0.001) >60 minutes after SAH compared with baseline values. The peak value of CK-MB correlated positively with the peak values of noradrenaline and adrenaline (r =0.730 and r =0.611, respectively). The peak value of troponin T also correlated positively with the peak values of noradrenaline and adrenaline (r =0.828 and r =0.792, respectively). Conclusions— These results suggest that the elevated activity of the sympathetic nervous system observed in the acute phase of SAH induced myocardial damage and contributed to the development of cardiac dysfunction.

Protective effect of urinary trypsin inhibitor on myocardial mitochondria during hemorrhagic shock and reperfusion.

ObjectiveTo examine the mitochondrial function in the myocardium after hemorrhagic shock and reperfusion and to evaluate the protective effect of urinary trypsin inhibitor (UTI) on mitochondria. DesignAnimal experiment. SettingUniversity research laboratory. SubjectsWistar rats receiving 50,000 units/kg/hr of UTI (n = 27; UTI group) and control rats (n = 26; control group). InterventionsRats were subjected to low-perfusion ischemia with the left ventricular systolic pressure maintained at 50 mm Hg for 60 mins by bleeding, followed by a 60-min reperfusion by transfusion of shed blood. UTI was infused continuously from 10 mins before bleeding. Cardiac function was measured before bleeding, after bleeding, and after transfusion; at each determination point, the myocardial contents of adenosine triphosphate (ATP), creatine phosphate (P-Cr), pyruvate (Pyr), and lactate (Lac) were measured enzymatically. The cytosolic phosphorylation potential (PP) as well as the redox potential of the oxidized form of nicotinamide adenine dinucleotide/reduced form of nicotinamide adenine dinucleotide couple in mitochondria (EhNAD+/NADH) and change of Gibbs free energy in ATP hydrolysis (&Dgr;GATP hydrolysis energy) were calculated. Measurements and Main ResultsCardiac function decreased during hemorrhagic shock but improved significantly in the UTI group after transfusion compared with the control group. Lac and the Lac/Pyr ratio were significantly lower in the UTI group than in the control group after transfusion. ATP and P-Cr were significantly higher in the UTI group than in the control group after transfusion. PP (×10 3 M−1), EhNAD+/NADH (x − 1 mV), and &Dgr;GATP hydrolysis (x − 1 kcal/mol) were 1.9 ± 0.4, 266 ± 4, and 9.7 ± 0.2, respectively, in the control group and 4.0 ± 0.9, 274 ± 5 and 13.0 ± 0.2, respectively, in the UTI group after transfusion (p < .001, p < .001, and p < .001, respectively). ConclusionsIn reperfusion after hemorrhagic shock, oxidative phosphorylation in myocardial mitochondria is impaired and energy production remains reduced, even after reperfusion. UTI contributed to the recovery of cardiac function after reperfusion, probably by reducing the severity of mitochondrial dysfunction during a state of shock and by maintaining energy production.

The Effect of Anti-Platelet Aggregation to Prevent Pressure Ulcer Development: A Retrospective Study of 132 Elderly Patients

Background: As the number of bedridden elderly patients increases, prevention of pressure ulcers is becoming a more important issue. However, an approach to this problem using medication has not been considered sufficiently in the clinical context. Objective: To test the hypothesis that anti-platelet aggregation therapy administered to the elderly patients may be helpful in preventing pressure ulcer formation, the medical records of 132 bedridden elderly patients were analyzed. In addition, the propensity of platelets to aggregate was also measured in some of the bedridden patients. Methods: Patients were divided into two groups, with pressure ulcers (group P, 52 patients) and without (group N, 80 patients). Subsequently, six factors defining the clinical characteristics age and gender, underlying disease, cause of being bedridden, level of consciousness, mobility and activity as defined on the Braden scale, and frequency of anti-platelet aggregation medication were investigated in groups P and N. In addition, physical findings (three factors): body mass index, blood pressure (BP), and heart rate were investigated in both groups. Furthermore, laboratory data (seven factors): total protein (TP), albumin, total cholesterol, hemoglobin (Hb), hematocrit (Hct), platelets, and platelet aggregation were compared between two groups. Results: There were no significant differences in clinical characteristics between the two groups with the exception of the frequency of anti-platelet aggregation medication (23.1% of group P vs. 40.0% of group N, χ2 = 4.06, p < 0.05). There was also no significant difference in physical findings except a difference between systolic and diastolic BP (48.4 mm Hg in group P vs. 57.1 mm Hg in group N, p < 0.01). Values of TP, albumin, Hb, and Hct in both groups were lower than the normal range, but there was no significant difference between the two groups. The platelet count was significantly greater in group P than in group N after lying supine (p < 0.03), and platelet aggregation in group P was significantly higher compared with group N (p < 0.03). Conclusions: Although our hypothesis must be tested by a randomized prospective trial, these results indicate that increased platelet aggregation is possibly associated with the development of pressure ulcers; therefore anti-platelet aggregation therapy may prevent their occurrence in bedridden elderly patients.

Pharmacokinetic characteristics of minocycline in debilitated elderly patients.

A pharmacokinetic study of minocycline was performed in 12 debilitated elderly patients who had suffered from acute bacterial respiratory infections. Serial intravenous administrations of 100 mg minocycline were performed at least 10 times (infused for 1 hour, every 12 hours). Blood samples were obtained at 0, 1, 3, and 10 hours after initiating the first and fifth dose and 1 hour after the ninth dose (total, 9 points). The serum concentrations of unchanged minocycline were measured using high-performance liquid chromatography. The obtained data were analyzed using a two-compartment model in 11 cases and a one-compartment model in 1 case. Other clinical data were also collected simultaneously. The mean age of the subjects was 82 +/- 6 years. The elimination half-lives at beta-phase averaged 25.0 +/- 16.4 hours, the volume of distribution averaged 32.9 +/- 13.4 L, and the total clearance averaged 1.14 +/- 0.49 L/h. The correlation coefficient between the expected trough concentration of minocycline in steady-state and the dose per 1 kg body weight was.54 (P =.06), suggesting that dosage should be adjusted by body weight when administered to debilitated elderly patients. The present data are considered to be important and clinically useful because little information is available concerning the pharmacokinetics of minocycline in elderly patients.

News from the IAG

This year marks the 50th anniversary of the International Association of Gerontology. To celebrate this watershed occasion, the IAG Executive, Regional Chairs and Presidents of member associations will have the opportunity to meet in December and consider future strategic directions for the association and contribute to a United Nations’ project, ‘Research Agenda on Ageing for the 21st Century’ (RAA-21). Invitations to the meeting have been distributed. The Salsomaggiore Therme has generously offered to provide full accommodation and board for delegates for the 3 days of the IAG meeting and travel grant assistance is being provided by the Novartis Foundation for Gerontology for presidents whose travel cannot be funded by their associations. A full day will be devoted to discussion of future strategic directions for the IAG. The next half day will be a joint consultation when the IAG representatives and a panel of experts with an ongoing involvement in developing the Research Agenda will convene. Participants will also include the Officer in Charge, Dr. Alexandre Sidorenko, and others from the UN Office on Ageing. The UN and Expert Panel will continue their deliberations for a further 2 days in order to draft the final Research Agenda. The United Nations Research Agenda project is supported by the Novartis Foundation for Gerontology and is convened by the IAG in support of the UN Programme on Ageing. The Second Congress Planning Committee Meeting for the 2001 Vancouver Congress convened by Dr. Gloria Gutman, President-Elect of IAG, will precede the gathering of presidents and regional chairs. Hence the 50th anniversary of the IAG will represent an occasion when it will be possible to build upon the proud history of the association and vigorously pursue the further development and achievements of national and global gerontological activities into the opening years of the new century. An agenda will be set for the meeting in Salsomaggiore, Italy, that we are confident will engender vigorous and positive consideration and debate about the IAG’s future directions and will set goals and objectives to guide the organization through the coming years.

Do Ketone Bodies Contribute to Protection against Damage Caused by Bothmyocardial Ischemia and Reperfusion Injury

Effects of ketone bodies on cardiac performance and mitochondrial energetics were investigated in experimental myocardial ischemia, with a special focus on the following reperfusion injury.