Ion channels in smooth muscle control coronary vascular tone, but the mechanisms require further investigation. The purpose of this study was to evaluate the functional role of KV1 channels on porcine coronary blood flow by using the selective antagonist correolide. KV1 channel gene transcripts were found in porcine coronary arteries, with KCNA5 (encoding KV1.5) being most abundant (P<0.001). Immunohistochemical staining demonstrated KV1.5 protein in the vascular smooth muscle layer of both porcine and human coronary arteries, including microvessels. Whole-cell patch clamp experiments demonstrated significant correolide-sensitive (1–10 µM) current in coronary smooth muscle. In vivo studies included direct intracoronary infusion of vehicle or correolide into a pressure-clamped left anterior descending artery of healthy swine (n=5 in each group) with simultaneous measurement of coronary blood flow. Intracoronary correolide (~0.3–3 µM targeted plasma concentration) had no effect on heart rate or systemic pressure, but reduced coronary blood flow in a dose-dependent manner (P<0.05). Dobutamine (0.3–10 µg/kg/min) elicited coronary metabolic vasodilation and intracoronary correolide (3 µM) significantly reduced coronary blood flow at any given level of myocardial oxygen consumption (P<0.001). Coronary artery occlusions (15 s) elicited reactive hyperemia and correolide (3 µM) reduced the flow volume repayment by approximately 30% (P<0.05). Taken together, these data support a major role for KV1 channels in modulating baseline coronary vascular tone and perhaps vasodilation in response to increased metabolism and transient ischemia.
Background: Ischemic heart disease is the leading cause of death in the United States, Canada, and worldwide. Severe disease is characterized by coronary artery occlusion, loss of blood flow to the myocardium, and necrosis of tissue, with subsequent remodeling of the heart wall, including fibrotic scarring. The current study aims to demonstrate the efficacy of quantitating infarct size via 2D echocardiographic akinetic length and 4D echocardiographic infarct volume and surface area as in vivo analysis techniques. We further describe and evaluate a new surface area strain analysis technique for estimating myocardial infarction (MI) size after ischemic injury. Methods: Experimental MI was induced in mice via left coronary artery ligation. Ejection fraction and infarct size were measured through 2D and 4D echocardiography. Infarct size established via histology was compared to ultrasound-based metrics via linear regression analysis. Results: 2D echocardiographic akinetic length (r = 0.76, p = 0.03), 4D echocardiographic infarct volume (r = 0.85, p = 0.008) and surface area (r = 0.90, p = 0.002) correlate well with histology. While both 2D and 4D echocardiography were reliable measurement techniques to assess infarct, 4D analysis is superior in assessing asymmetry of the left ventricle and the infarct. Strain analysis performed on 4D data also provides additional infarct sizing techniques, which correlate with histology (surface strain: r = 0.94, p < 0.001, transmural thickness: r = 0.76, p = 0.001). Conclusions: 2D echocardiographic akinetic length, 4D echocardiography ultrasound and strain provide effective in vivo methods for measuring fibrotic scarring after MI.
Introduction Measuring hemodynamic characteristics of injured limbs is paramount to early identification of potentially damaging ischemic conditions, but can often prove difficult attributable to a multitude of factors. Here, we present an in vivo optical imaging technique to characterize pulsatile blood flow quality through the distal extremity in multiple animal models that replicate the signs of distal extremity ischemia. The purpose of this study is to examine the feasibility of the optical imaging technique and relevance to hemodynamic complications such as acute compartment syndrome (ACS) and nonobvious hemorrhage. Materials and Methods In one pig and six mice, three different methods were used to create ischemic conditions in the lower extremity, producing symptoms similar to what is observed in ACS. In each condition, perfusion to the distal extremity was measured with the hemodynamic detection device (HDD; Odin Technologies), an optical assessment tool for perfusion and blood flow quality. Results We observed a profound decrease in extremity perfusion immediately after onset of ischemia in all three models. In the porcine model, the HDD’s measurements demonstrated similar characteristic flow between the various measurement locations. After the tourniquet was applied, the HDD revealed a 95% decrease in normalized perfusion value (npv) while the intracompartmental pressure rose from 5 to 52 mmHg (a 47mmHg increase). After the tourniquet was removed during reperfusion, the normalized blood flow returned to baseline and the intracompartmental pressure dropped from 20 to 6 mmHg in less than 5 minutes. For each mouse, the HDD test leg demonstrated a measurement of 0.97 npv before femoral ligation and 0.05 npv after femoral ligation, an 89% decrease (P < .01) in flow. Pulsed-wave Doppler ultrasound (PWDU) measurements on the test leg had pre-ligation measurement of 0.84 npv and a post-ligation measurement of 0.001 npv, a 99% decrease. These PWDU measurements revealed almost complete stoppage of blood flow during ischemia, followed by a substantial increase after the femoral artery ligation was removed. Conclusions Here, we show that a novel, optics-based sensing system can be used to diagnose and assess ACS in animal models. This technology is comparable to other standards used to monitor ACS and nonobvious hemorrhage and may also be a plausible alternative to prolonged invasive monitoring of patients with sustained extremity trauma.
Low-flow digital vaporizers commonly utilize a syringe pump to directly administer volatile anesthetics into a stream of carrier gas. Per animal welfare recommendations, animals are warmed and monitored during procedures requiring anesthesia. Common anesthesia and physiological monitoring equipment include gas tanks, anesthetic vaporizers and stands, warming controllers and pads, mechanical ventilators, and pulse oximeters. A computer is also necessary for data collection and to run equipment software. In smaller spaces or when performing field work, it can be challenging to configure all this equipment in limited space.The goal of this protocol is to demonstrate best practices for use of a low-flow digital vaporizer using both compressed oxygen and room air, along with an integrated mechanical ventilator, pulse oximeter, and far infrared warming as an all-inclusive anesthesia and physiological monitoring suite ideal for rodents.
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