Hyperchloremic metabolic acidosis during bipolar transurethral resection of the prostate: a report of two cases.

Compared with monopolar transurethral resection of the prostate (TURP), which requires electrolyte-free irrigation fluid, normal saline can be used as the irrigation solution in bipolar and laser TURP. The risk of TURP syndrome and severe electrolyte disturbance is minimized when normal saline is used as the irrigation fluid. However, the use of isotonic saline also causes acid-base imbalance and electrolyte disturbance. We experienced two patients who developed hyperchloremic metabolic acidosis during bipolar TURP. After proper intervention, hemodynamic instability resolved, and laboratory test results normalized. Anesthesiologists must pay attention to acid-base and electrolyte status when rapid absorption of excessive isotonic solution is suspected, even during bipolar and laser TURP, which use normal saline as the irrigation fluid.

Correlation between the Perfusion Index and Intraoperative Hypothermia: A Prospective Observational Pilot Study.

Background and Objectives: We examined the association between the baseline perfusion index (PI) and changes in intraoperative body temperature during general anesthesia. The PI reflects the peripheral perfusion state. The PI may be associated with changes in body temperature during general anesthesia because the degree of redistribution of body heat from the central to the peripheral compartment varies depending on the peripheral perfusion state. Materials and Methods: Thirty-eight patients who underwent brain surgery were enrolled in this study. The baseline PI and body temperature of the patients were measured on entering the operating room. Body temperature was recorded every 15 min after induction of anesthesia using an esophageal temperature probe. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for intraoperative hypothermia. Results: Eighteen patients (47 %) developed hypothermia intraoperatively. The baseline PI was significantly lower among patients in the hypothermia group (1.8 ± 0.7) than among those in the normothermia group (3.0 ± 1.2) (P < 0.001). The baseline PI and body temperature were independently associated with intraoperative hypothermia (PI: odds ratio [OR], 0.270; 95% confidence interval [CI], 0.105-0.697; P = 0.007, baseline body temperature: OR, 0.061; 95% CI, 0.005-0.743; P = 0.028). Conclusions: This study showed that low baseline PI was the factor most related to the development of intraoperative hypothermia. Future studies should consider the PI as a predictor of intraoperative hypothermia.

Identification of Novel Non-secosteroidal Vitamin D Receptor Agonists with Potent Cardioprotective Effects and devoid of Hypercalcemia.

Vitamin D regulates many biological processes, but its clinical utility is limited by its hypercalcemic effect. Using a virtual screening platform to search novel chemical probes that activate the vitamin D signaling, we report discovery of novel non-steroidal small-molecule compounds that activate the vitamin D receptor (VDR), but are devoid of hypercalcemia. A lead compound (known as VDR 4-1) demonstrated potent transcriptional activities in a VDR reporter gene assay, and significantly ameliorated cardiac hypertrophy in cell culture studies and in animal models. VDR 4-1 also effectively suppressed secondary hyperparathyroidism in 1α-hydroxylase knockout mice. In contrast to 1α,25-dihydroxyvitamin D3 (1,25-D3 or calcitriol), a naturally occurring VDR agonist, VDR 4-1 therapy even at high doses did not induce hypercalcemia. These findings were accompanied by a lack of upregulation of calcium transport genes in kidney and in the gut providing a mechanism for the lack of hypercalcemia. Furthermore, VDR 4-1 therapy significantly suppressed cardiac hypertrophy and progression to heart failure in both vitamin D deficient and normal mice without inducing significant hypercalcemia. In conclusion, we have identified a unique VDR agonist compound with beneficial effects in mouse models of hyperparathyroidism and heart failure without inducing significant hypercalcemia.

Abnormal calcium handling and exaggerated cardiac dysfunction in mice with defective vitamin d signaling.

AIM: Altered vitamin D signaling is associated with cardiac dysfunction, but the pathogenic mechanism is not clearly understood. We examine the mechanism and the role of vitamin D signaling in the development of cardiac dysfunction. METHODS AND RESULTS: We analyzed 1α-hydroxylase (1α-OHase) knockout (1α-OHase-/-) mice, which lack 1α-OH enzymes that convert the inactive form to hormonally active form of vitamin D. 1α-OHase-/- mice showed modest cardiac hypertrophy at baseline. Induction of pressure overload by transverse aortic constriction (TAC) demonstrated exaggerated cardiac dysfunction in 1α-OHase-/- mice compared to their WT littermates with a significant increase in fibrosis and expression of inflammatory cytokines. Analysis of calcium (Ca2+) transient demonstrated profound Ca2+ handling abnormalities in 1α-OHase-/- mouse cardiomyocytes (CMs), and treatment with paricalcitol (PC), an activated vitamin D3 analog, significantly attenuated defective Ca2+ handling in 1α-OHase-/- CMs. We further delineated the effect of vitamin D deficiency condition to TAC by first correcting the vitamin D deficiency in 1α-OHase-/- mice, followed then by either a daily maintenance dose of vitamin D or vehicle (to achieve vitamin D deficiency) at the time of sham or TAC. In mice treated with vitamin D, there was a significant attenuation of TAC-induced cardiac hypertrophy, interstitial fibrosis, inflammatory markers, Ca2+ handling abnormalities and cardiac function compared to the vehicle treated animals. CONCLUSIONS: Our results provide insight into the mechanism of cardiac dysfunction, which is associated with severely defective Ca2+ handling and defective vitamin D signaling in 1α-OHase-/- mice.

Vitamin D signaling pathway plays an important role in the development of heart failure after myocardial infarction.

Accumulating evidence suggests that vitamin D deficiency plays a crucial role in heart failure. However, whether vitamin D signaling itself plays an important role in cardioprotection is poorly understood. In this study, we examined the mechanism of modulating vitamin D signaling on progression to heart failure after myocardial infarction (MI) in mice. Vitamin D signaling was activated by administration of paricalcitol (PC), an activated vitamin D analog. Wild-type (WT) mice underwent sham or MI surgery and then were treated with either vehicle or PC. Compared with vehicle group, PC attenuated development of heart failure after MI associated with decreases in biomarkers, apoptosis, inflammation, and fibrosis. There was also improvement of cardiac function with PC treatment after MI. Furthermore, vitamin D receptor (VDR) mRNA and protein levels were restored by PC treatment. Next, to explore whether defective vitamin D signaling exhibited deleterious responses after MI, WT and VDR knockout (KO) mice underwent sham or MI surgery and were analyzed 4 wk after MI. VDR KO mice displayed a significant decline in survival rate and cardiac function compared with WT mice after MI. VDR KO mice also demonstrated a significant increase in heart failure biomarkers, apoptosis, inflammation, and fibrosis. Vitamin D signaling promotes cardioprotection after MI through anti-inflammatory, antifibrotic and antiapoptotic mechanisms.

Doxercalciferol, a pro-hormone of vitamin D, prevents the development of cardiac hypertrophy in rats.

BACKGROUND: Activated vitamin D analog, paricalcitol, has been shown to attenuate the development of cardiac hypertrophy in Dahl salt sensitive (DSS) rats. To determine whether an antihypertrophic effect is class specific, we tested if doxercalciferol (a pro-hormone vitamin D2 analog) could also attenuate the development of cardiac hypertrophy in DSS rats. METHODS AND RESULTS: Male DSS rats were fed a high salt (HS) diet for 6 weeks beginning at 6 weeks of age. Doxercalciferol was administered intraperitoneally at 150 ng, 3 times per week (Monday, Wednesday, Friday) for 6 weeks. Pathological and echocardiographic findings demonstrated that rats on HS diet with doxercalciferol administration had significant decrease in cardiac hypertrophy and improved cardiac function compared to the HS + vehicle. In addition, there was a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level with doxercalciferol treatment. Doxercalciferol also significantly reduced the level of protein kinase C-α (PKCα) suggesting that PKC-mediated cardiac hypertrophy may be associated with vitamin D deficiency. CONCLUSIONS: Administration of doxercalciferol attenuated the development of HS diet induced cardiac hypertrophy and cardiac dysfunction in DSS rats.

Mitochondria to nucleus translocation of AIF in mice lacking Hsp70 during ischemia/reperfusion.

Heat shock protein 70 (Hsp70) has been shown to have an anti-apoptotic function, but its mechanism is not clear in heart. In this study, we examined the effect of Hsp70 deletion on AIF-induced apoptosis during ischemia/reperfusion (I/R) in vivo. Although Hsp70 KO and WT mice demonstrated similar amounts of AIF released from mitochondria after I/R surgery, Hsp70 KO mice showed a significantly greater increase in apoptosis, larger infarct size, and decreased cardiac output. There was also a significant fourfold increase in the nuclear accumulation of AIF in Hsp70 KO mice compared with WT mice. Treatment with 4-AN (4-amino-1,8-napthalimide, 3 mg/kg), a potent inhibitor of PARP-1, which is a critical regulator of AIF-induced apoptosis, significantly blocked the release of AIF from mitochondria and the translocation of AIF into the nuclei after I/R in both WT and Hsp70 KO mice. In addition, 4-AN treatment resulted in a significant inhibition of apoptosis, a reduction of infarct size, and attenuated cardiac dysfunction in both WT and Hsp70 KO mice after I/R. The anti-apoptotic function of Hsp70 occurs through the inhibition of AIF-induced apoptosis by blocking the mitochondria to nucleus translocation of AIF. PARP-1 inhibition improves cardiac function by blocking AIF-induced apoptosis.

Extracorporeal shock wave-induced proliferation of periosteal cells.

The cambium cells of the periosteum are an important cell source for select tissue engineering/regenerative medicine applications due to their osteogenic and chondrogenic potential. However, the cambium layer is only 2-5 cells thick, which complicates its harvest, and the low cell number limits its suitability for certain applications. Extracorporeal shock waves (ESWs) have been reported to cause periosteal osteogenesis following cambium layer thickening. This study quantified the proliferation of cambium cells in the femur and tibia of adult rats following ESW treatment at two different energy flux densities. Four days after application of ESWs, there was a significant (3- to 6-fold) increase in cambium layer thickness and cell number. Proliferation was seen with an energy flux density as low as 0.15 mJ/mm(2). The tibial cambium cells were more proliferative than those of the femur, with the cells closest to the ESW source proliferating the most. Within the thickened periosteum, α-smooth muscle actin and von Willebrand Factor expression were upregulated, suggesting a vascular role in ESW osteogenesis. Bone formation was seen within the stimulated periosteum at day 4. We propose that non-invasive ESWs can be used to rapidly stimulate cambium cell proliferation, providing a larger cell population for use as a progenitor cell source for tissue engineering applications, than can normally be provided by periosteum.