Yasuko Tomizawa

Clinical benefits and risk analysis of topical hemostats: a review.

A variety of local hemostats including absorbable gelatin sponge, collagen hemostat, and oxidized cellulose are commercially available. Local hemostats are applied when cautery, ligature, or other conventional hemostatic method is impractical. Proper handling is essential to control bleeding and only the required amount should be used, even though the hemostat is expected to dissolve promptly. A dry local hemostat absorbs body fluid of several times its own weight and expands postoperatively. Therefore, when an absorbable hemostatic agent is retained on or near bony or neural spaces, the minimum amount should be left after hemostasis is achieved. Documentation is important with regard to the hemostat used, including the name of the agent, site, and amount. This information is used as a reference in the interpretation of postoperative diagnostic images, since retained hemostat may sometimes mimic an abscess or recurrent tumor. The antigenicity of collagen is known to be low because of homology. When the safety of collagen was evaluated, the incidence of positive reactions was reported as 3.0%, and collagen may cause allergic reactions. Minimum inflammation without strong foreign body reactions or blockade of healing is desirable after the use of local hemostats. Strong foreign body reactions, chronic inflammation, and infections can cause granuloma formation after local hemostat use. By using local hemostats, it is possible to improve the condition of the patient, reduce complications, and lower direct and indirect costs.

Bilateral Versus Unilateral Internal Mammary Revascularization in Patients With Diabetes

Background—This historical cohort study evaluated the benefit of bilateral internal mammary artery (BIMA) grafts in coronary bypass grafting (CABG) for patients with diabetes. Methods and Results—We performed elective, isolated, primary, multiple CABG using skeletonized internal mammary artery (IMA) grafts for multivessel disease in 1131 patients, 467 (41.3%) of whom had type 2 diabetes mellitus. The early and long-term results were compared between 277 patients with diabetes using single IMA (SIMA) grafts and 190 using BIMA grafts (median follow-up, 8.1 years). Hospital mortality was similar in both groups. Early patency rate of all grafts was significantly higher using BIMA than using SIMA (97.7% versus 93.8%, P =0.0012). Survival rates were not significantly different between SIMA and BIMA groups. Late cardiac mortality was significantly higher in patients with low ejection fraction (0.4 or lower) compared with preserved ejection fraction (higher than 0.4) (P =0.0001). In patients with preserved ejection fraction, 10-year survival rate was significantly higher using BIMA than using SIMA (87.8±3.5% versus 75.2±3.4%, P =0.04), and 10-year all death–free or repeat CABG or recurrent myocardial infarction–free rate was significantly higher using BIMA than using SIMA (86.6±3.6% versus 69.0±3.7%, P =0.0086). The hazard ratio for all death or repeated CABG or recurrent myocardial infarction in patients with preserved ejection fraction was markedly lower in the BIMA group (0.53; 95% CI, 0.31 to 0.9; P =0.019). Conclusions—Skeletonized BIMA grafts are beneficial in coronary revascularization for diabetic patients with preserved ejection fraction but have limited survival benefit for those with reduced ejection fraction attributable to high cardiac mortality.

Permissive range of hypercapnia for improved peripheral microcirculation and cardiac output in rabbits

Objectives:Permissive hypercapnia improves outcomes in patients with respiratory failure, most likely because of a reduction in ventilator-induced lung injury. Because hypercapnia is a potent vasoactive stimulus, adequate tissue perfusion and oxygen delivery to dilated microvessels may be restored. We examined how Paco2 affects microvascular changes, hemodynamics, and cardiac output in rabbits. We evaluated the permissive range of Paco2 required for maintenance of the peripheral circulation. Design:Prospective experimental animal study. Setting:Animal research laboratory. Subjects:A total of 31 Japanese domestic white rabbits. Interventions:The animals were anesthetized with pentobarbital. An ear chamber was prepared to examine blood vessels by intravital microscopy. The rabbits were mechanically ventilated with air, oxygen, and CO2. The values of Paco2 were adjusted to about 20 (hypocapnia), 40 (normocapnia), 60, 80, 100, 125, 150, and >250 mm Hg (hypercapnia). After stabilization at each Paco2 level, microvascular changes were recorded with a microscope-closed video camera to permit analysis of arteriolar diameter and blood flow. Measurements and Main Results:The pH and heart rate decreased and mean blood pressure increased progressively as the Paco2 was increased. When Paco2 was increased from 20 to 80 mm Hg, vessel diameter, blood-flow velocity, and blood-flow rate increased markedly. Cardiac output increased slightly. When Paco2 exceeded 100 mm Hg, all of these variables decreased. When Paco2 exceeded 150 mm Hg, all variables were significantly lower than the control values (p < .01). Conclusion:Intravital microscopic visualization of the rabbit ear microcirculation showed that 150 mm Hg is the permissive upper limit of acute hypercapnia with respect to maintenance of the peripheral microcirculation.

Cardiac rehabilitation and artificial heart devices

Recently, cardiac rehabilitation has gained popularity in Japan because beneficial effects on patients’ prognosis have been reported. Another reason is that cardiac rehabilitation has been covered by health insurance since 1988 in Japan. Currently, cardiac rehabilitation is covered for the diseases of angina pectoris, acute myocardial infarction, chronic heart failure (CHF), peripheral arterial disease, and diseases of the aorta and after open-heart surgery. Left ventricular assist devices (LVADs) are sometimes used in patients with progressive CHF symptoms to provide circulatory support, because in most of these patients heart failure does not improve with application of medical therapy, intra-aortic balloon pumping, or a percutaneous cardiopulmonary system. Modern VAD control systems are compact, allowing patients to carry them around without difficulty. Since patient management at the outpatient clinic has become possible, patients are able to expand the scope of their activities. Early active rehabilitation in patients implanted with a LVAD improves their condition, favorably impacts the clinical course while they await heart transplantation, and also improves posttransplant recovery. Exercise therapy is one of the important components in comprehensive cardiac rehabilitation. Exercise therapy is important to improve the quality of life of patients with LVADs. Appropriate exercise therapy is effective for patients with various cardiac conditions who undergo diverse treatments and is practiced actively by many patients. In order to facilitate cardiac rehabilitation safely and effectively for patients with serious conditions, education for health care professionals is essential. In this review, we describe the concept of rehabilitation followed by cardiac rehabilitation for patients with heart failure, patients after open-heart surgery, and patients with implanted LVADs.

Microcirculatory Responses to Acupuncture Stimulation and Phototherapy

BACKGROUND: Acupuncture stimulation and phototherapy have been reported to have analgesic effects and improve the microcirculation. However, few studies have directly examined changes in peripheral blood vessels, either quantitatively or objectively. We assessed the responses of arteriolar blood flow to acupuncture stimulation and phototherapy under direct vision to examine the effects of these treatments. METHODS: We used 40 rabbits with a rabbit ear chamber attached to the auricle. The rabbit ear chamber was fixed to the auricle under a dissecting microscope. Arterioles were selected and observed with the use of a microscope video camera. Pentobarbital was injected IV. The trachea was intubated and spontaneous respiration was maintained. Rabbits were randomly assigned to receive acupuncture stimulation (acupuncture group, n = 10), near-infrared lamp irradiation (lamp group, n = 10), near-infrared low-powered laser irradiation (laser group, n = 10), or no irradiation (control group, n = 10). In the acupuncture group, an acupuncture needle was placed in the auricle for 20 min. The lamp group repeatedly received 1 s of near infrared irradiation (1540 mW) followed by 4 s of treatment cessation. The laser group continuously received 60 mW of laser irradiation. In the lamp and laser groups, the auricle (same site as that of the acupuncture needles in the acupuncture group) was irradiated for 10 min with a contact probe. Arteriolar diameter and blood flow velocity were measured at baseline and for 60 min after acupuncture or irradiation treatment. Blood flow rate was calculated by multiplying the blood flow velocity by the cross-sectional area of the vessels. RESULTS: Arteriolar diameter significantly increased to 131% ± 14% in the acupuncture group (P < 0.005), 129% ± 19% in the lamp group (P < 0.005), and 128% ± 11% in the laser group (P < 0.005) when compared with the pretreatment value (100%). Maximum values were reached 20 min after the end of the acupuncture stimulation, and 10 min after the end of lamp and laser irradiation. The three groups showed significant increases in arteriolar diameter when compared with the control group (P < 0.005). Blood flow velocity and blood flow rate showed similar trends to arteriolar diameter. Treatment effect persisted for 40–50 min after the end of stimulation and irradiation. CONCLUSIONS: Acupuncture stimulation and phototherapy were directly confirmed to increase the diameter and blood flow velocity of the peripheral arterioles. Acupuncture stimulation and phototherapy, associated with minimal systemic and local side effects, can enhance the microcirculation and may be a useful supportive treatment for diseases caused by poor peripheral blood flow.

Comparison of the cross-linking characteristics of porcine heart valves fixed with glutaraldehyde or epoxy compounds

The concerns about currently available bioprosthetic heart valves are calcification, long-term durability, and functional and hemodynamic performance. These concerns are all more or less related to the cross-linking reagents, glutaraldehyde or formaldehyde, used in fixing bioprostheses. To address these concerns, the authors undertook the development of a porcine heart valve cross-linked with an epoxy compound. This study compared the cross-linking characteristics, shrink temperature, and moisture content of porcine heart valves fixed with epoxy compounds or glutaraldehyde. Two types of epoxy compounds, Denacol EX-313 and EX-810, or a 0.625% glutaraldehyde were used to fix the porcine aortic valves procured from a slaughter house. Samples of each group were removed at various elapsed fixation times. The shrink temperature and moisture content of the valvular leaflet and distinct layers of aortic wall of each sample were measured. Fresh porcine aortic valve was used as a control. It was found that the shrink temperature of the glutaraldehyde leaflet was the highest, whereas the moisture content of the EX-313 leaflet was the greatest among the three test groups. No significant difference in shrink temperature was observed among the epoxy compound fixed inner, middle, outer, and entire aortic walls. This implied that the cross-linking density of the epoxy compound valve was uniform throughout the entire aortic wall. The same also was observed for the glutaraldehyde fixed aortic wall.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo and in vitro evaluation of gelation and hemostatic properties of a novel tissue-adhesive hydrogel containing a cross-linkable polymeric micelle.

There is a clinical requirement for a local hemostat that arrests bleeding from both suture holes and cross-sectional surfaces of parenchymatous organs. A novel tissue-adhesive hydrogel was prepared that contains a cross-linkable polymeric micelle consisting of poly(ethylene glycol)-poly(DL-lactide) block polymers, and, by means of a rheometer, the factors that affect the hydrogels gelation properties was clarified. The storage modulus and the gelation time greatly depended on both the pH and the concentrations of both the polymeric micelle and polyallylamine solutions. Furthermore, the hemostatic potential of the hydrogel in a mouse hemostasis model was evaluated under optimal conditions as determined by the rheometer. The average amount of bleeding from the mouse liver was 172.9 mg (S.D. 69.7 mg, N = 7) in the control experiments, whereas it was 20.1 mg (s.d. 13.2, N = 7) when the hydrogel was applied to the wound (p = 0.002). The result demonstrated that the novel synthetic hydrogel possessed a significant hemostatic potential as a local hemostat.

A simple hemostasis model for the quantitative evaluation of hydrogel-based local hemostatic biomaterials on tissue surface

Several hemostat hydrogels are clinically used, and some other agents are studied for safer, more facile, and more efficient hemostasis. In the present paper, we proposed a novel method to evaluate local hemostat hydrogel on tissue surface. The procedure consisted of the following steps: (step 1) a mouse was fixed on a cork board, and its abdomen was incised; (step 2) serous fluid was carefully removed because it affected the estimation of the weight gained by the filter paper, and parafilm and preweighted filter paper were placed beneath the liver (parafilm prevented the filter papers absorption of gradually oozing serous fluid); (step 3) the cork board was tilted and maintained at an angle of about 45 degrees so that the bleeding would more easily flow from the liver toward the filter paper; and (step 4) the bleeding lasted for 3 min. In this step, a hemostat was applied to the liver wound immediately after the liver was pricked with a needle. We found that (1) a careful removal of serous fluid prior to a bleeding and (2) a quantitative determination of the amount of excess aqueous solution that oozed out from a hemostat were important to a rigorous evaluation of hemostat efficacy. We successfully evaluated the efficacy of a fibrin-based hemostat hydrogel by using our method. The method proposed in the present study enabled the quantitative, accurate, and easy evaluation of the efficacy of local hemostatic hydrogel which acts as tissue-adhesive agent on biointerfaces.

Effects of colloid resuscitation on peripheral microcirculation, hemodynamics, and colloidal osmotic pressure during acute severe hemorrhage in rabbits.

We examined the effects of hydroxyethyl starch (HES) on the microcirculation, hemodynamics, and colloidal osmotic pressure in a rabbit model of hemorrhagic shock. A total of 40 rabbits was anesthetized with pentobarbital and isoflurane, and they were mechanically ventilated. An ear chamber was prepared to examine blood vessels by intravital microscopy. Shock was induced by removing nearly half of the circulating blood volume. Twenty rabbits received 20 mL of HES by intravenous infusion immediately after blood letting. Additional HES was then administered intravenously to a total volume of 100 mL. The other 20 rabbits (control) were intravenously given 40 mL of lactated Ringer’s solution (LR), followed by additional LR to a total volume of 200 mL, administered under the same conditions as HES. After blood letting, arteriolar diameter decreased similarly in the the HES and LR groups (HES, 40.5% ± 14.8% of the baseline value versus LR, 43.3% ± 13.1%). After the completion of infusion, arteriolar diameter significantly recovered to 90.8% ± 10.2% of the baseline value in the HES group as compared with only 62.6% ± 10.7% in the LR group (P < 0.005). Recovery of arterial blood flow velocity and blood flow rate was also significantly better in the HES group than in the LR group (P < 0.005). Mean arteriolar pressure, central venous pressure, and plasma colloid osmotic pressure after the completion of infusion were significantly greater in the HES group than in the LR group (P < 0.005). We conclude that intravenous infusion of HES effectively maintains the microcirculation, hemodynamics, and colloidal osmotic pressure in a rabbit model of acute severe hemorrhage.

Survival benefit of exclusive use of in situ arterial conduits over combined use of arterial and vein grafts for multiple coronary artery bypass grafting.

BACKGROUND The purpose of this study was to evaluate mortality after coronary artery bypass grafting (CABG) comparing the use of only in situ arterial grafts with the use of arterial and venous conduits. METHODS AND RESULTS From April 1985 to March 1999, 1159 patients with multivessel disease underwent elective, isolated, primary, multiple CABG with at least one in situ arterial conduit. Patients who were on chronic dialysis, had active malignant disease, or had free arterial conduits were excluded. The long-term results were compared between 532 patients who had CABG using only in situ arterial conduits (group A; mean follow-up, 7.8 years) and 627 patients who underwent CABG using in situ arterial conduits and saphenous vein grafts (group B; mean follow-up, 10.3 years). Actuarial survival and freedom from cardiac death were determined by the Kaplan-Meier method. Propensity score was included in the Cox multivariable regression model for adjustment of selection bias. Survival at 10 years after surgery was 81.4% in group A and 76.9% in group B (P=0.11). Freedom from cardiac death at 10 years was 93.4% in group A and 90.4% in group B. Hazard ratio for cardiac death was significantly lower in group A (0.61; 95% confidence interval, 0.38 to 1.00; P=0.05). CONCLUSIONS Our data suggest that the exclusive use of in situ arterial grafts in CABG achieves significantly better long-term survival compared with combined use of arterial and vein grafts.