Importance of luxury flow for critically ill patients receiving a left ventricular assist system

The presence of a significant organ dysfunction does not immediately exclude patients from consideration for treatment with a left ventricular assist system (LVAS). However, in treating morbid circulatory shock patients with multiple organ failure, it is important to know the preoperative and postoperative factor or factors related to the recovery of the damaged organ function. In this study, we retrospectively analyzed patients receiving a LVAS at our institution and tried to determine the important factors related to the survival of patients with multisystem failure. Twenty-seven patients who underwent LVAS placement at Saitama Medical School Hospital between 1993 and 2003 were included in this study. The preoperative risk factors analyzed were renal dysfunction, respiratory dysfunction, hepatic dysfunction, the existence of active infection, and the combination of all four factors. As a postoperative factor, the pump flow index (mean LVAS pump flow during the first 2 weeks after LVAS surgery divided by the body surface area) was analyzed. None of the analyzed preoperative factors could predict survival after LVAS surgery, but a pump flow index of less than 2.5 l/min/m² had a significant relationship with death after LVAS surgery. Further analysis revealed that all the patients with a pump flow index of 3.0 l/min/m² or more could overcome preoperative organ dysfunction. Congestive heart failure patients with multisystem failure need luxury pump flow for successful LVAS surgery; this factor could be especially important in device selection and postoperative management.     

Negative chronotropic actions of endothelin-1 on rabbit sinoatrial node pacemaker cells

1. The effects of endothelin-1 (ET-1) on sinoatrial (SA) node preparations of the rabbit heart were studied by means of whole-cell clamp techniques.
2. ET-1 at 1 nM slowed the spontaneous beating activity and rendered half of the cells quiescent. At a higher concentration of 10 nM, the slowing and cessation of spontaneous activity were accompanied by hyperpolarization.
3. In voltage-clamp experiments, ET-1 decreased the basal L-type Ca²⁺ current (I_Ca(L)) dose-dependently with a half-maximal inhibitory concentration (EC₅₀) of 0.42 nM and maximal inhibitory response (E_max) of 49.5%. The delayed rectifying K⁺ current (I_K) was also reduced by 33.2±11.1% at 1 nM. In addition, an inwardly rectifying K⁺ current was activated by ET-1 at higher concentrations (EC₅₀=4.8 nM). These ET-1-induced changes in membrane currents were abolished by BQ485 (0.3 μM), a highly selective ET_A receptor antagonist.
4. When I_Ca(L) was inhibited by ET-1 (1 nM), subsequent application of 10 μM ACh showed no additional decrease in I_Ca(L), suggesting the involvement of cyclic AMP in the effects of ET-1 on I_Ca(L). In contrast, 1 nM ET-1 further decreased I_Ca(L) in the presence of 10 μM ACh, suggesting that ET-1 activates some additional mechanism(s) which inhibit I_Ca(L). The ET-1-induced I_Ca(L) inhibition was abolished by protein kinase A inhibitory peptide (PKI, 20 μM) or H-89 (5 μM). However, the I_Ca(L) inhibition was not affected by methylene blue (10 μM), suggesting a minor role for cyclic GMP in the effect of ET-1 under basal conditions.
5. ET-1 failed to inhibit I_Ca(L) when the pipette contained GDPβS (200 μM). However, incubation of the cells with pertussis toxin (PTX, 5 μg ml⁻¹, >6 h) only reduced the ET-1-induced inhibition to 21.5±9.5%, whereas it abolished the inhibitory effect of ACh on I_Ca(L).
6. Intracellular perfusion of 8-bromo cyclicAMP (8-Br cyclicAMP, 500 μM) attenuated, but did not abolish the inhibitory effect of ET-1 on I_Ca(L). This 8-Br cyclicAMP-resistant component (17.5±14.4%, n=20) was not affected by combined application of 8-Br cyclicAMP with 8-bromo cyclicGMP (500 μM), ryanodine (1 μM) or phorbol-12-myristate-13-acetate (TPA; 50 nM).
7. In summary, ET-1 exerts negative chronotropic effects on the SA node via ET_A-receptors. ET-1 inhibits both I_Ca(L) and I_K, and increases background K⁺ current. The inhibition of I_Ca(L) by ET-1 is mainly due to reduction of the cyclicAMP levels via PTX-sensitive G protein, but some other mechanism(s) also seems to be operative.

     

Studies of effects of anticancer agents in combination with/without hyperthermia on metastasized human bladder cancer cells in chick embryos using the polymerase chain reaction technique

Cultivated T24 cells derived from a human bladder cancer were inoculated into the chorioallantoic membrane vein of chick embryos. Hyperthermic treatment was performed following injection of anticancer agents 3 days after the inoculation of the T24 cells. DNA samples were obtained from the livers of the chick embryos, and the polymerase chain reaction technique was used to amplify a DNA fragment specific to the human -globin gene. The Southern hybridization method was used to evaluate the inhibitory effects of anticancer agents in combination with/without hyperthermia on T24 cells metastasized to the liver. The hyperthermia exerted an inhibitory effect on the growth of the T24 cells in the livers of the chick embryos, and this was dependent on the thermal dose. The antitumor effects of hyperthermia performed at 42.5° C for 20 min and at 43.0° C for 10 min were evidenced by 69.2% an 82.0% inhibition of the growth of the metastasized T24 cells, respectively, as compared with the growth of untreated T24 cell. Hyperthermia performed at 42.5° C for 10 min alone produced 26.7% tumor growth inhibition, and these conditions for hyperthermia were subsequently used as a criterion for evaluating the effects of its combination with various anticancer agents. Adriamycin (20 g/egg) alone, mitomycin C (10 g/egg) alone, carboplatin (10 g/egg) alone, and cisplatin (10 g/egg) alone produced 13.5%, 58.9%, 27.3%, and 29.1% tumor growth inhibition, respectively. Adriamycin and mitomycin C applied in combination with hyperthermia showed additive inhibitory effects on the growth of the metastasized T24 cells in this chick embryo model.     

PCNA immunostaining combined with AgNOR staining in esophageal squamous cell carcinoma to identify patients with a poor prognosis

Immunostaining of the proliferating cell nuclear antigen (PCNA) provides important information about cell kinetics and is easily performed on routinely obtained formalin-fixed, paraffin-embedded materials. We report herein the results of a retrospective study on PCNA staining in esophageal cancer undertaken to determine its significance. As this study indicated that immunoreactivity was preserved in specimens fixed within 24 h, only 31 specimens from surgical patients were available for this investigation. The mean PCNA index of the patients without invasion to the adventitia (35.7±17.9) was significantly lower than that of those with invasion to the adventitia or neighboring structures (49.7±14.5), while the PCNA index did not correlate with other clinicopathologic parameters such as histologic type, lymph node metastases, or prognosis. However, when an analysis of PCNA staining was combined with an analysis of argyrophilic nucleolar organizer region (AgNOR) staining, a correlation with prognosis was found. In fact, seven patients with a high PCNA index (44) and AgNOR count (6) had a significantly poorer prognosis than the remaining 22 (P=0.0014), and six of these seven patients died within 2 years. These results indicate that this combined evaluation may be useful for the identification of patients with a poor prognosis among those undergoing surgery for esophageal squamous cell carcinoma.     

Renal microcirculation]

The blood flow to the kidney averages about 20% of the cardiac output and the renal circulation affects urine formation. The renal microcirculation is unique. Glomerular circulation is mainly regulated by two resistance arterioles, the afferent arteriole and the efferent arteriole. Two capillary beds are arranged in series between the arterial and venous circulation. Many experimental findings show that each arteriole has a different sensitivity to various stimuli. Moreover, several anatomic characteristics of the renal circulation display heterogeneity. Several regional differences in the renal microcirculation may subserve the excretory function of the kidney. Technological advances now permit direct observation of renal arterioles and measurements of microvascular pressure, flows and resistances. In this mini review, we introduce 1) characteristics of renal circulation, 2) techniques for study of renal microcirculation, 3) effects of angiotensin II on the renal microvasculature, and 4) future directions for the study of renal microcirculation.     

Control of mesenteric arterial tone in vitro in humans and rats

The majority of the findings concerning arterial physiology and pathophysiology originate from studies with experimental animals, while only limited information exists about the functional characteristics of human arteries. Therefore, the aim of the present work was to compare the control of vascular tone in vitro in mesenteric arterial rings of corresponding size (outer diameter 0.75–1 mm) from humans and Wistar-Kyoto rats. The relaxations to acetylcholine (ACh) were clearly less marked in the mesenteric arteries of humans when compared with rats. How-ever, when calcium ionophore A23187 was used as the vasodilator, the endothelium-mediated relaxations did not significantly differ between these species. The NO synthase inhibitor N ^G-nitro-l-arginine methyl ester (l-NAME) attenuated the relaxations to ACh and A23187 in both groups. The endothelium-independent relaxations to the β-adrenoceptor agonist isoprenaline and the nitric oxide (NO)-donor nitroprusside were somewhat lower in human arteries, while vasodilation induced by the K⁺ channel opener cromakalim was similar between humans and rats. Arterial contractile sensitivity to noradrenaline and serotonin was slightly lower in human vessels, whereas contractile sensitivity to KCl was similar between these species. The contractions induced by cumulative addition of Ca²⁺ with noradrenaline as the agonist were effectively inhibited in both groups by the calcium channel blocker nifedipine, the effect of which was clearly more pronounced in human arteries. In conclusion, the control of vascular tone of isolated arteries of corresponding size from humans and rats appeared to be rather similar. The most marked differences between these species were the impaired endothelium-mediated dilation to ACh and the more pronounced effect of nifedipine on the Ca²⁺-induced contractions in human arteries. Received: 1 October 1998 / Accepted: 4 January 1999     

Assessment of hepatic graft injury by graft effluent in rodents: N-acetyl-β-glucosaminidase and type III procollagen peptide

We studied the significance of N-acetyl--glucosaminidase (-NAG) and type III procollagen peptide (P-III-P) in the effluent of rodent hepatic grafts. After total hepatectomy, the livers were preserved in chilled, lactated Ringer's solution and then divided into five groups (n=10 each): group 1, 4 h preservation only; group 2, 4 h preservation and rewarming; group 3, 6 h preservation only; group 4, 6 h preservation and rewarming; and group 5, minimal preservation only. The -NAG of groups 2 and 4 was significantly higher than that of groups 1 and 3 (0.98±0.5 U/l vs 0.21±0.12 U/l; P<0.01 and 1.76±0.67 U/l vs 0.38±0.25 U/l, respectively; P<0.01), while that of group 4 was significantly higher than that of group 2 (1.76±0.67 U/l vs 0.98±0.50 U/l; P<0.05). The P-III-P of group 4 was significantly higher than that of group 2 (0.133±0.008 U/ml vs 0.110±0.015 U/ml; P<0.01). We conclude that -NAG is a novel parameter of parenchymal and nonparenchymal cells, while P-III-P reflects the integrity of the hepatic sinusoidal extracellular matrix.     

Neuro-ophthalmologic signs in a recurrent cerebellar astrocytoma after 48 years

This is a report of the neuro-ophthalmologic and neuropathologic findings in a patient with a recurrence of a cerebellar astrocytoma after 48 years. Dr. Harvey Cushing performed the initial operation at the Peter Bent Brigham Hospital in 1928. This patient was included in his classic review: "Experiences with the Cerebellar Astrocytomas--A critical review of seventy-six cases." The extensive documentation of the original tumor by Cushing, the unusually long period of 48 years for the recurrence of the tumor, and the opportunity to examine the patient and postmortem brain specimen in detail make this a unique case report.