Update on Perioperative Pediatric Pulmonary Hypertension Management.

Pediatric pulmonary hypertension is a disease that has many etiologies and can present anytime during childhood. Its newly revised hemodynamic definition follows that of adult pulmonary hypertension: a mean pulmonary artery pressure >20 mmHg. However, the pediatric definition stipulates that the elevated pressure must be present after the age of three months. The definition encompasses many different etiologies, and diagnosis often involves a combination of noninvasive and invasive testing. Treatment often is extrapolated from adult studies or based on expert opinion. Moreover, although general anesthesia may be required for pediatric patients with pulmonary hypertension, it poses certain risks. A thoughtful, multidisciplinary approach is needed to deliver excellent perioperative care.

How We Would Treat Our Own Pulmonary Hypertension if We Needed to Undergo Cardiac Surgery.

Pulmonary hypertension (PH) is a disease that has many etiologies and is particularly prevalent in patients presenting for cardiac surgery, with which it is linked to poor outcomes. This manuscript is intended to provide a comprehensive review of the impact of PH on the perioperative management of patients who are undergoing cardiac surgery. The diagnosis of PH often involves a combination of noninvasive and invasive testing, whereas preoperative optimization frequently necessitates the use of specific medications that affect anesthetic management of these patients. The authors postulate that a thoughtful, multidisciplinary approach is required to deliver excellent perioperative care. Furthermore, they use an index case to illustrate the implications of managing a patient with pulmonary hypertension who presents for cardiac surgery with cardiopulmonary bypass.

Blood use for transvenous lead extractions at a high-volume center.

BACKGROUND: Transvenous lead extractions (TLEs) have increased in number due to an increased prevalence of cardiac implantable devices. Bleeding complications associated with TLEs can be catastrophic, and many institutions order blood components to be available in the procedure room. There are few studies supporting or refuting this practice. We evaluated transfusion rates for TLEs at a single, high-volume center to assess the need for having blood in the procedure room. STUDY DESIGN AND METHODS: Patients undergoing TLEs from April 2010 to February 2019 were identified from our institutional database. The percentage of patients transfused intraoperatively, the number of units transfused, and the reasons for transfusion were determined from the database and by manual chart review. RESULTS: A total of 473 patients underwent a TLE during this time frame. Of these, only 17 patients (3.6%) received a red blood cell (RBC) transfusion. Ten of the 17 patients received RBCs secondary to preoperative anemia. Of the remaining seven patients, only four patients received more than 2 RBC units, and only one received more than 10 RBC units. No patient received more than 2 RBC units or any plasma or platelets in the past 4 years. CONCLUSION: Due to improvements in procedural techniques, advent of accessible remote blood allocation systems, and changes in transfusion practice (e.g., electronic crossmatch), routinely having blood components in the procedure room for every TLE may be an outdated practice for high-volume centers.

Vasopressin-mediated enhancement of adrenergic vasoconstriction involves both the tyrosine kinase and the protein kinase C pathways.

BACKGROUND: Vasopressin is frequently used to treat catecholamine-resistant vasodilatory shock. It enhances the vasoconstrictor effects of catecholamines at concentrations of vasopressin that have none or only minimal intrinsic pressor effects. However, the vascular mechanisms underlying this combined pharmacological approach have not been fully elucidated. METHODS: We used isometric tension measurements in vascular rings to investigate potential cellular mechanisms. Vascular rings (0.2 mm diameter) were harvested from the superior mesenteric artery of Wistar rats (2 to 4 months of age). Dose-response relationships were derived for vasopressin (VP) and norepinephrine (NE), in the absence and presence of a subpressor dose of VP (10(-9) M). The contribution of tyrosine kinase (TK), the TK pathway proteins SRC and PYK2, as well as protein kinase C (PKC) were determined by measuring the modulating influence of specific inhibitors on the pressor response to NE (10(-5) M) alone and the augmented pressor response to VP (10(-9) M). RESULTS: VP (10(-9) M) had only minimal pressor effect alone (10% of maximal response), but significantly increased the E(max) response to NE (587.8 ± 40.7 vs 331.2 ± 10.4 mg). TK inhibition completely abolished the pressor response to NE (100% vs 1.0% 0.5%) and the augmented VP response alone (100% vs 2.0% ± 1.01%). Both responses were significantly, but equally, decreased by SRC inhibition (63% ± 4.0% and 69% 1.0%). In contrast, inhibition of the TK molecule PYK2 with salicylate had differential inhibitory effects on the vasoconstrictor responses. Salicylate caused a greater inhibition of VP-induced augmented NE response in comparison with NE alone (62.1% ± 7% and 15% ± 2%). Inhibition of either the µ or γ PKC isoform significantly decreased both responses, but the magnitude of the inhibition was significantly different for each isoform. Inhibition of the γ PKC isoform significantly decreased the vasoconstriction responses to both NE and VP plus NE (82.9 ± 3.9 vs 32.8 ± 3.8). Inhibition of the µ PKC isoform significantly decreased both responses and completely abolished the VP-augmented response to NE. CONCLUSION: These data are consistent with a central role for TK in mediating both the NE response and the VP-augmented response. Moreover, PYK2 and the µ and γ isoforms of PKC seem to play a preferential role in mediating the augmented VP response. The apparent divergent roles of these pathways in mediating NE- versus VP-augmented pressor responses could potentially lead to new targeted therapies in catecholamine-resistant shock.

Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness.

Advanced glycation end-products (AGEs) initiate cellular inflammation and contribute to cardiovascular disease in the elderly. AGE can be inhibited by Alagebrium (ALT), an AGE cross-link breaker. Moreover, the beneficial effects of exercise on aging are well recognized. Thus, we investigated the effects of ALT and exercise (Ex) on cardiovascular function in a rat aging model. Compared to young (Y) rats, in sedentary old (O) rats, end-systolic elastance (Ees) decreased (0.9±0.2 vs 1.7±0.4mmHg/µL, P<0.05), dP/dt(max) was attenuated (6054±685 vs 9540±939mmHg/s, P<0.05), ventricular compliance (end-diastolic pressure-volume relationship (EDPVR)) was impaired (1.4±0.2 vs 0.5±0.4mmHg/µL, P<0.05) and diastolic relaxation time (tau) was prolonged (21±3 vs 14±2ms, P<0.05). In old rats, combined ALT+Ex (4weeks) increased dP/dt(max) and Ees (8945±665 vs 6054±685mmHg/s, and 1.5±0.2 vs 0.9±0.2 respectively, O with ALT+Ex vs O, P<0.05 for both). Diastolic function (exponential power of EDPVR and tau) was also substantially improved by treatment with Alt+Ex in old rats (0.4±0.1 vs 0.9±0.2 and 16±2 vs 21±3ms, respectively, O with ALT+EX vs O, P<0.05 for both). Pulse wave velocity (PWV) was increased in old rats (7.0±0.7 vs 3.8±0.3ms, O vs Y, P<0.01). Both ALT and Ex alone decreased PWV in old rats but the combination decreased PWV to levels observed in young (4.6±0.5 vs 3.8±0.3ms, O with ALT+Ex vs Y, NS). These results suggest that prevention of the formation of new AGEs (with exercise) and breakdown of already formed AGEs (with ALT) may represent a therapeutic strategy for age-related ventricular and vascular stiffness.

Serum fatty acid synthase as a marker of pancreatic neoplasia.

Markers of early pancreatic cancer and its precursors are needed to improve the uniformly poor prognosis of this disease. Fatty acid synthase (FAS) catalyzes the synthesis of long-chain fatty acids and is overexpressed in most human solid tumors. We therefore evaluated serum FAS as a marker of pancreatic adenocarcinoma. FAS expression patterns in primary pancreatic adenocarcinomas, intraductal papillary mucinous neoplasms (IPMN), and chronic pancreatitis tissues were analyzed by immunohistochemistry. Serum FAS levels were determined by ELISA in 102 patients with pancreatic adenocarcinomas, in 42 patients with IPMNs, in 27 patients with chronic pancreatitis, and in 39 healthy control subjects. FAS protein was overexpressed in the ductal epithelium of 343 of 399 primary pancreatic adenocarcinomas (86.0%) and 28 of 30 IPMNs (93.3%), and in the islet and ductal cells in 3 of 54 chronic pancreatitis tissues (5.6%), whereas normal ductal epithelium lacked FAS expression. Serum FAS levels were significantly higher in patients with pancreatic ductal adenocarcinoma (first quartile median, 22.0; 4.5 ng/mL), in patients with IPMNs (20.7; 9.4 ng/mL), and in patients with chronic pancreatitis (31.1; 11.9 ng/mL) than in healthy controls (0; 0 ng/mL). FAS levels declined postoperatively in 8 of 9 patients with pancreatic adenocarcinoma and elevations of their preoperative serum FAS. In conclusion, serum FAS levels are elevated in patients with pancreatic cancer and IPMNs and are associated with neoplastic overexpression of FAS.