Infusion Of Nitroprusside Research Articles

Clinical impact of perfusion balloon for ST-segment elevated myocardial infarction: RYUSEI study

Abstract Background Drug-eluting stents have significantly contributed to reducing mortality in patients with ST-segment elevation myocardial infarctions (STEMIs), but slow flow/no-reflow phenomenon and in-stent restenosis are still clinical problems. On the other hand, perfusion balloons (PBs) can compress thrombi and ruptured plaque for long inflation without ischemia and can be used as a delivery device for infusion of nitroprusside to distal risk area during ballooning. Purpose We conducted RYUSEI (Reduction of risk bY perfUsion balloon for ST-segment Elevated myocardial Infarction) study to evaluate whether PBs before stenting are more effective than conventional stenting for STEMIs. Methods We divided consecutive patients with STEMIs who underwent optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) into PB group who were treated with PBs before stenting and the conventional PCI (CP) group. In PB group, we inflated PB at the culprit lesion for five minutes to compress thrombi and ruptured plaque as a pre-stent lesion modification. In addition, an intra-coronary injection of nitroprusside (total dose: 120 µg; slow bolus injection of 24 µg/5mL every minute [5 times]) into the distal vascular bed to the culprit lesion through the PB was performed during a 5-minute PB ballooning. We compared clinical results including slow flow/no-reflow phenomenon, OCT findings, and one-year clinical events including cardiac death, target vessel-related myocardial infarctions, target lesion revascularization and stent thromboses between the two groups. Results We finally analyzed 34 patients in PB group and 90 in CP group. After propensity score matching, PB and CP groups consisted of 23 patients, respectively. In the propensity score-matched cohort, there were no significant differences of the patients’ backgrounds and lesion and procedural characteristics between the two groups. In the cohort, regarding post PCI angiographic and OCT findings, the incidence of slow flow/no-reflow phenomenon and maximum protrusion area detected by OCT were significantly lower (P=0.047 and P=0.019, respectively) and TIMI flow grade 3 was significantly higher (P=0.022) in the PB group than CP group while the other parameters were similar (Table). Kaplan-Meier analysis revealed a significantly better one-year clinical outcome in PB group than CP group (p=0.038) (Figure). Conclusions The RYUSEI study revealed a pre-stent lesion modification in addition to nitroprusside infusion using PB is useful to achieve better clinical course in STEMI patients.Post PCI Angiographic and OCT FindingsComparison of One-year Clinical Outcome

MITRACLIP TREATMENT FOR CARDIOGENIC SHOCK DUE TO ACUTE MITRAL REGURGITATION IN A PATIENT WITH POSTINFARCTION PAPILLARY MUSCLE RUPTURE

Abstract A 85–year–old woman presented to ED with worsening dyspnea for 24 hours; no other related symptom. Her medical history included hypertension, dyslipidemia, type 2 DM and surgical coronary revascularization 13 years before for multiple critical coronary artery disease (LIMA to LAD and sequential SVG to PDA and OM branch). The ECG promptly revealed a subacute infero–lateral STEMI. Transthoracic echocardiography (TTE) showed inferior and postero–lateral wall akinesia with severely reduced left ventricle ejection fraction (LVEF), mildly reduced right ventricle systolic function and severe mitral regurgitation (MR) due to posterior papillary muscle (PM) rupture (Fig.1). Clinical scenario was complicated by pulmonary edema and cardiogenic shock treated with diuretics and sodium nitroprusside infusion, non–invasive ventilation and IABP insertion. Urgent coronary angiography revealed a thrombotic occlusion of the venous graft for OM branch. Surgical correction was excluded due to hemodynamic instability. Graft occlusion was treated with manual thromboaspiration, balloon dilatations and abciximab infusion. After an initial stabilization, transesophageal echocardiography (TEE) was performed confirming severe MR resulting from rupture of one head of a bifid posterior PM (red arrows, Fig.1) and prolapse of the anterior leaflet combined with restrictive systolic movement of the posterior leaflet due to wall motion abnormalities. 3 days later a transcatheter mitral valve edge–to–edge repair (MTEER) was performed using a MitraClip device (1 XTR clip and 1 NTR clip, Fig.2). TEE with 3D and TrueVue vision confirmed the correct placement of clips (Fig.3), a mild–to–moderate residual MR, absence of significant transmitral gradient and a mildly reduced LVEF. No clinical events were reported during recovery; patient was discharged after 2 weeks. Conclusion MTEER is an established therapy for reducing degenerative and functional MR. Little data is available on its use in the setting of PM rupture. This rare complication of AMI carries a mortality rate of 80% during the first week without surgical correction but more than half of patients are excluded because of prohibitive operative risk. TEER may be an alternative for these patients. In this case report we described the utility of MTEER in the setting of cardiogenic shock secondary to acute ischemic MR with papillary muscle partial rupture. This procedure can be useful with acceptable safety and procedural success.

Clinical Impact of Perfusion Balloon for ST-Segment Elevated Myocardial Infarction: RYUSEI Study

Drug-eluting stents have significantly contributed to reducing mortality in patients with ST-segment elevation myocardial infarctions (STEMIs), but slow flow/no-reflow phenomenon (SFNR) and in-stent restenosis are still clinical problems. On the other hand, perfusion balloons (PBs) can compress thrombi and ruptured plaque for long inflation without ischemia and can be used as a delivery device for infusion of nitroprusside to distal risk area during ballooning. We conducted RYUSEI (Reduction of risk bY perfUsion balloon for ST-segment Elevated myocardial Infarction) study to evaluate whether PBs before stenting are more effective than conventional stenting for STEMIs. We divided consecutive patients with STEMIs who underwent optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) into PB group who were treated with PBs (Ryusei®; Kaneka Medix Corporation, Osaka, Japan) before stenting and the conventional PCI (CP) group. We compared clinical results including SFNR, OCT findings, and clinical events between the two groups. We finally analyzed 34 patients in PB group and 90 in CP group. After propensity score matching, PB and CP groups consisted of 23 patients, respectively. In the propensity score-matched cohort, SFNR and maximum protrusion area detected by OCT were significantly lower (P=0.047 and P=0.019) and TIMI flow grade 3 higher (P=0.022) in the PB group than CP group. Kaplan-Meier analysis revealed a significantly better clinical outcome in PB group than CP group (p=0.038). In conclusion, the RYUSEI study revealed a pre-stent lesion modification in addition to nitroprusside infusion using PB is useful to achieve better clinical course in STEMI patients.

Functional sympatholysis of Neuropeptide Y-mediated vasoconstriction in humans

Metabolic inhibition of sympathetic vasoconstriction (functional sympatholysis) is essential for adequate perfusion of skeletal muscle during exercise. Functional sympatholysis occurs primarily through post-junctional attenuation of norepinephrine and α-adrenergic-mediated vasoconstriction, though other non-adrenergic neurotransmitters are co-released with norepinephrine. Neuropeptide Y (NPY) is a neurotransmitter that elicits robust vasoconstriction and is co-released with norepinephrine during exercise in an intensity dependent manner. Evidence from animal models indicate that NPY is sensitive to metabolic inhibition, however metabolic inhibition of NPY-mediated vasoconstriction has not been tested in humans. We tested the hypothesis that NPY-mediated vasoconstriction would be attenuated during handgrip exercise in humans. In 10 healthy adults (7M:3F, age: 30±7 years, BMI: 24±5) we measured forearm blood flow (Doppler ultrasound), blood pressure (brachial artery catheter), and calculated changes in forearm vascular conductance (FVC) to local intra-arterial infusions of phenylephrine (PE; α1-agonist) or NPY (Y1R-agonist) during 1) intra-arterial infusion of sodium nitroprusside (SNP; nitric oxide donor) to serve as a non-metabolic vasodilatory control or 2) dynamic rhythmic handgrip exercise (EX; 15% maximal voluntary contraction). The vasoconstrictor responses to PE and NPY were quantified as a percent ΔFVC during each condition (SNP vs. EX) and were compared by two-way RM-ANOVA. The magnitude of sympatholysis (ΔFVC during exercise expressed as a percent of control) for PE and NPY was compared by a paired t-test. As expected, the vasoconstrictor response to PE was attenuated during handgrip exercise compared to SNP (ΔFVC: SNP: -50±24 vs. EX: -17±9 %; p=0.002). Similarly, NPY-mediated vasoconstriction was blunted during handgrip exercise compared to SNP (ΔFVC: SNP: -32±22 vs. EX: -11±7 %; p=0.029). There was no difference in the magnitude of sympatholysis between PE and NPY (PE: 68±18, NPY: 52±34 %; p=0.28). These data indicate that NPY-mediated vasoconstriction is sensitive to metabolic inhibition in humans, and the magnitude of sympatholysis is not different from α1-adrenergic vasoconstriction. Funding: NIH R00HL153777. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Divergent Vasodilator Mechanisms to Endothelial-Dependent Agonists with Advancing Age

Introduction: Microvascular function is maintained by a number of vasodilating factors, with nitric oxide (NO) and endothelial hyperpolarizing factors (EDHF) predominating. Advancing age is an independent risk factor in the development of cardiovascular disease, and NO-mediated vasodilation declines, or is unchanged, depending on the vascular bed examined, number of cardiovascular risk factors, or specific endothelial-dependent agonist used. Mechanisms contributing to cutaneous microvascular dysfunction with age have been attributed largely to reductions in NO signaling, but the role of EDHF-mediated dilation, particularly to acetylcholine (ACh), remains unclear. The purpose of this study was to determine the endothelial mechanisms contributing to age-induced cutaneous microvascular function and compare cutaneous microvascular function responses to those from isolated adipose arteriole preparations. We hypothesized that cutaneous microvascular vasodilation to ACh in older adults will be mediated primarily by EDHFs relative to young adults and that isolated adipose arteriole preparations will corroborate these findings. Methods: Four intradermal microdialysis fibers were placed in the skin of the ventral forearm of 9 young (3F/6M; 29±7 yrs) and 3 older adults (3F/0M; 59±11 yrs) for infusion of Ringer’s solution; L-NAME (10 mM), an NO synthase inhibitor; tetraethylammonium chloride (TEA; 50 mM), a non-specific K+ channel inhibitor; and a combination of L-NAME and TEA. Laser Doppler flowmetry and brachial mean arterial pressure were measured during infusion of ACh (10 mM and 100 mM) and in response to local heating to 39°C. Maximal vasodilation was assessed with heating to 43°C and infusion of sodium nitroprusside (28 mM). Adipose resistance arterioles for pressure myography were obtained from a gluteal biopsy or from surgical discard tissue, which were pre-constricted (ET-1), and ACh responses (10−9–10−4 M) were assessed in the presence of the above inhibitors. Cutaneous vascular conductance (CVC) and isolated arteriole responses are presented as % maximum vasodilation. Results: In response to local heating in young adults, L-NAME reduced vasodilator magnitude (Ringers 69.0±18.1% vs. L-NAME 30.3±12.1%; p< 0.05) while TEA did not have any effect (69±18% vs. 49±28%; p=0.20). Combined L-NAME and TEA reduced vasodilation (69±18% vs. 19±6%; p<0.05). Conversely, vasodilator magnitude to ACh was not different across the Ringers, L-NAME, or TEA sites (p=0.93-0.94), while combined inhibition of NOS and K+ channels with L-NAME and TEA, respectively, reduced vasodilator responsiveness (p<0.05). In isolated resistance arterioles, there were no differences in %max dilation to ACh across inhibitor sites (p=0.19) in young adults. In older adults, neither independent nor combined inhibition of NOS or K+ channels impacted vasodilator responses to local heating, while vasodilator magnitude to ACh was most impacted by combined inhibition with L-NAME and TEA (83±14% vs. 32±15%; p<0.05). Conclusion: Our data demonstrate that vasodilator plasticity in response to local heating is divergent with advancing age, relying on non-NO or K+ mechanisms relative to young adults, while NO and K+ mechanisms are suffcient to maintain ACh-mediated vasodilation. These findings further support the concept of diversity in vasodilator mechanisms within the microvasculature. NHLBI K99-HL161491 (WEH), K08-HL150340 (JJM), R01-HL160752 (JKF), R01-HL133029 (AB), and NICHD R01-HD099340 (MJD). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

What Is the Role of the Carotid Baroreflex in Exaggerating the Exercise Pressor Reflex in Male UCD-Type 2 Diabetes Mellitus Rats?

Previous studies have shown that exercise evokes an excessive increase in blood pressure in individuals with type 2 diabetes mellitus (T2DM), which is mediated, in part, by an altered exercise pressor reflex. Importantly, in healthy individuals the arterial baroreflex modulates the pressor response to exercise; however, the effects of T2DM on this modulatory effect of the baroreflex remain unclear. Therefore, the purpose of this study was to characterize the arterial baroreflex function in T2DM rats and to determine whether the carotid baroreflex plays a role in exaggerating the exercise pressor reflex. We hypothesized that T2DM rats would present a baroreflex dysfunction that likely contributes to the exaggerated pressor response during muscle contraction. Experiments were performed on adult (8 ± 2 months old), male University of California Davis (UCD)-T2DM ( n=7; body weight: 640 ± 43 g) and healthy Sprague-Dawley rats ( n=3; body weight: 485 ± 29 g). Female rats were not included in this study because they become diabetic when they are much older (>10 months old). Cardiac baroreflex function was characterized in anesthetized T2DM and healthy rats using the modified Oxford technique, which involved sequential bolus infusions of sodium nitroprusside (10 μg/kg) and phenylephrine (10 μg/kg) to induce blood pressure decreases and increases, respectively. Overall cardiac baroreflex gain (i.e., slope of the relationship between systolic blood pressure and R-R interval) was calculated using logistic regression, while gains to blood pressure falling and rising were calculated separately using piecewise and linear regression. The role of the carotid baroreflex in exaggerating the exercise pressor reflex was tested by statically contracting the hindlimb muscles for 30 s after surgical sinoaortic denervation (SAD) in decerebrated T2DM ( n=1; body weight: 555 g) and healthy ( n=1; body weight: 519 g) rats. Carotid barointact T2DM ( n=8; body weight: 521 ± 38 g) and healthy rats ( n=8; body weight: 482 ± 56 g) were included as controls. The pressor responses were calculated as a change (Δ) in peak mean arterial pressure during 30 s contraction relative to baseline. Data are presented as mean ± SD. T2DM rats presented with lower overall baroreflex sensitivity (T2DM: 0.07 ± 0.02 ms/mmHg, healthy: 0.61 ± 0.81 ms/mmHg, p=0.044), as well as sensitivity to increases in blood pressure (T2DM: 0.14 ± 0.10 ms/mmHg , healthy: 0.28 ± 0.15 ms/mmHg, p=0.049) compared to healthy controls. In contrast, cardiac baroreflex gain during decreases in blood pressure were not different between groups (T2DM: 0.16 ± 0.07 ms/mmHg, healthy: 0.10 ± 0.06 ms/mmHg, p=0.109). Notably, SAD did not alter blood pressure response to muscle contraction in the T2DM rat (SAD: Δ32 mmHg vs barointact: Δ32 ± 12 mmHg), but evoked an exaggerated blood pressure response in healthy rat (SAD: Δ34 mmHg vs barointact: Δ12 ± 3 mmHg). Our preliminary findings suggest that despite an attenuated cardiac baroreflex function in T2DM rats, specifically during acute increases in blood pressure, carotid baroreflex dysfunction may not contribute significantly to the exaggerated exercise pressor reflex in diabetes. This project was supported by NIH R01 HL144723. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Nitroprusside Combined with Leg Raise at the Time of Right Heart Catheterization to Differentiate Precapillary from Other Hemodynamic Forms of Pulmonary Hypertension: A Single-Center Pilot Study.

Pulmonary hypertension (PH) can arise from several distinct disease processes, with a percentage presenting with combined pre- and postcapillary pulmonary hypertension (cpcPH). Patients with cpcPH are unsuitable candidates for PH-directed therapies due to elevated pulmonary capillary wedge pressures (PCWPs); however, the PCWP is dynamic and is affected by both preload and afterload. Many patients that are diagnosed with cpcPH are hypertensive at the time of right heart catheterization which has the potential to increase the PCWP and, therefore, mimic a more postcapillary-predominant phenotype. In this small pilot study, we examine the effect of nitroprusside combined with dynamic preload augmentation with a passive leg raise maneuver in hypertensive cpcPH patients at the time of right heart catheterization to identify a more precapillary-dominant PH phenotype. Patients that met the criteria of PCWP ≤ 15 mmHg with nitroprusside infusion and PCWP ≤ 18 mmHg with nitroprusside infusion and simultaneous leg raise were started on pulmonary vascular-targeted therapy. Long-term PH therapy was well tolerated, with increased six-minute walk distance, improved WHO functional class, decreased NT-proBNP, and improved REVEAL 2.0 Lite Risk Score in this precapillary-dominant PH phenotype. This small study highlights the importance of characterizing patient physiology beyond resting conditions at the time of right heart catheterization.

Eight weeks of treatment with mineralocorticoid receptor blockade does not alter vascular function in individuals with and without type 2 diabetes.

Aldosterone has been suggested to be involved in the microvascular complications observed in type 2 diabetes. We aimed to investigate the effect of mineralocorticoid receptor (MR) blockade on endothelial function in individuals with type 2 diabetes compared to healthy controls. We included 12 participants with type 2 diabetes and 14 controls. We measured leg hemodynamics at baseline and during femoral arterial infusion of acetylcholine and sodium nitroprusside before and 8 weeks into treatment with MR blockade (eplerenone). Acetylcholine infusion was repeated with concomitant n-acetylcysteine (antioxidant) infusion. No difference in leg blood flow or vascular conductance was detected before or after the treatment with MR blockade in both groups and there was no difference between groups. Infusion of n-acetylcysteine increased baseline blood flow and vascular conductance, but did not change the vascular response to acetylcholine before or after treatment with MR blockade. Skeletal muscle eNOS content was unaltered by MR blockade and no difference between groups was detected. In conclusion, we found no effect of MR blockade endothelial function in individuals with and without type 2 diabetes. As the individuals with type 2 diabetes did not have vascular dysfunction, these results might not apply to individuals with vascular dysfunction.

Abstract P197: Dietary Quality Determined by Healthy Eating Index-2015 and Endothelial Function in Healthy Adults

The Healthy Eating Index (HEI) is a measure of diet quality based on Dietary Guidelines for Americans and developed in collaboration with the US Department of Health and Human Services and the US Department of Agriculture. Clinical interest in HEI has increased due to its association with obesity, inflammatory biomarkers and risk of coronary heart disease and stroke. Indeed, higher HEI-2015 score has been linked with reduced cardiovascular risk, morbidity, and mortality. Endothelial dysfunction, particularly impaired endothelium-dependent vasodilation, is a central etiological factor underlying cardiovascular risk and events. We and others have previously demonstrated that diets high in saturated fat and other proatherogenic diets are associated with endothelial vasodilator dysfunction. It is currently unknown whether HEI-2015 dietary score is associated with endothelial function. If so, assessing dietary quality based on HEI-2015 may provide targeted nutritional guidance for enhancing vascular health and mitigating cardiovascular risk. The aim of this study was to determine whether HEI-2015 score is associated with endothelial vasodilator function in healthy adults. Using data from 4-day dietary records, HEI-2015 scores were determined in 103 adults (65 M/38 F; age 44-68 years) free of overt cardiometabolic disease. The HEI-2015 score is based on 13 components summed to yield a total score from 0 to 100; higher score representing higher diet quality. The adults were stratified by HEI-2015 score quartiles: Q1: HEI < 52.5 (n=25; 23 M/2 F); Q2: HEI 52.6-59.1 (n=26; 14 M/12 F); Q3: HEI 59.2-66.0 (n=26; 15 M/11 F); and Q4: HEI > 66.0 (n=26; 13 M/13 F). Endothelium-dependent vasodilation was determined by forearm blood flow (FBF) (via plethysmography) responses to intra-arterial infusion of acetylcholine (ACh: 4.0, 8.0, and 16.0 μg/100 mL tissue/min) and sodium nitroprusside (NTP: 1.0, 2.0, and 4.0 μg/100 mL tissue/min). There were no significant differences in endothelium-dependent vasodilation across the HEI-2015 score quartiles. FBF blood responses to ACh were remarkably similar between Q1 (5.1±0.2 to 13.0±0.7 mL/100 mL tissue/min), Q2 (4.3±0.2 to 12.1±0.7 mL/100 mL tissue/min), Q3 (4.4±0.2 to 13.0±0.7 mL/100 mL tissue/min) and Q4 (4.5±0.2 to 14.4±0.6 mL/100 mL tissue/min). Moreover, HEI scores were not significantly associated with the vasodilator response to either ACh (r=0.15, P=0.13) or NTP (r=-0.04; P=0.72). In summary, although diet quality determined by HEI-2015 score has been shown to be associated with increased risk of cardiovascular disease and events, HEI-2015 was not associated endothelial function in mid-life and older adults. Given the established experimental and pathophysiological evidence linking between diet, endothelial vasodilator function and cardiovascular risk, HEI-2015 score is not a sensitive dietary indicator/biomarker of vascular function.

The role of T-type calcium channels in elderly human vascular function: A pilot randomized controlled trial.

Endothelial dysfunction develops with age and may precede cardiovascular disease. Animal data suggest that T-type calcium channels play an important role in endothelial function, but data from humans are lacking. This study included 15 healthy, sedentary, elderly males for a double blinded, randomized controlled trial. For 8weeks, they were given 40mg/day of either efonidipine (L- and T-type calcium channel blocker (CCB)) or nifedipine (L-type CCB). Vascular function was evaluated by graded femoral arterial infusions of acetylcholine (ACh; endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator) both with and without co-infusion of N-acetylcysteine (NAC; antioxidant). We measured leg blood flow and mean arterial pressure and calculated leg vascular conductance to evaluate the leg vascular responses. Despite no significant change in blood pressure in either group, we observed higher leg blood flow responses (Δ 0.43±0.45l/min, P=0.006) and leg vascular conductance (Δ 5.38±5.67ml/min/mmHg, P=0.005) to intra-arterial ACh after efonidipine, whereas there was no change in the nifedipine group, and no differences between groups. We found no upregulation of endothelial nitric oxide synthase in vastus lateralis muscle biopsies within or between groups. Smooth muscle cell responsiveness was unaltered by efonidipine or nifedipine. Intravenous co-infusion of NAC did not affect endothelium-dependent vasodilatation in either of the CCB groups. These results suggest that 8weeks' inhibition of T- and L-type calcium channels augments endothelium-dependent vasodilatory function in healthy elderly males. Further studies are required to elucidate if T-type calcium channel inhibition can counteract endothelial dysfunction.

Utilizing venous occlusion plethysmography to assess vascular effects: A study with buloxibutid, an angiotensin II type 2 receptor agonist.

Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open-label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra-arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 μg/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8-3.2 μg/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra-arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3-200 μg/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230-320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra-arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.

Abstract 13309: Severe Cardiomyopathy as Harbinger of Multisystem Inflammatory Syndrome From Epstein Barr Infection

Introduction: Multisystem inflammatory syndrome in adults (MIS-A) is a rare condition characterized by multiple organ injury after a viral infection. Features include fever, elevated inflammatory markers, evidence of acute viral infection, and at least three of the following clinical criteria: peri/myocarditis or acute ventricular dysfunction, rash, encephalopathy, shock, and gastrointestinal symptoms. This is a case of nonischemic cardiomyopathy (NICMP) as a MIS-A manifestation after an Epstein-Barr viral (EBV) infection. Description of Case: A 38 year-old female, with a recent pneumonia, presented with two weeks of fever, dyspnea, hemoptysis, fatigue, and right leg swelling. Initial ECG showed sinus tachycardia. Laboratory testing showed leukocytosis 15.5k/uL, NT pro BNP 6470 pg/mL, C-reactive protein 234 mg/L, lactic acid 3.7 mmol/L, creatinine 1.5 mg/dL (baseline 0.7 mg/dL), AST 372 U/L, ALT 658 U/L. RSV, influenza, COVID-19, HIV, hepatitis B/C, and urine antigens were undetected. Imaging showed deep vein thrombosis in right leg veins and bilateral pulmonary emboli with infarcts. Heparin infusion was started. A transthoracic echocardiogram showed biventricular systolic failure with an ejection fraction of 20%. Coronary angiography showed no coronary artery disease. Cardiac MRI showed dilated NICMP with minimal late gadolinium enhancement. The nadir of her cardiac index was 1.2 L/min/m 2. She was started on nitroprusside infusion for early-stage cardiogenic shock. Extensive workup for thrombophilia, autoimmune, amyloidosis, infectious causes were all normal except for an elevated EBV early antigen IgG which indicated past infection within a few months, aligning with patient’s reported pneumonia symptoms before presentation. She clinically improved and was bridged to heart failure guideline directed medical therapy and apixaban on discharge. Discussion: Though MIS-A has been reportedly associated with COVID-19, EBV can cause MIS, with severe cardiomyopathy, nephropathy, hepatopathy, and pulmonary infarcts requiring intensive cardiac care, in a normal young adult.

Fractional-order PID controller for blood pressure regulation using genetic algorithm

In this paper, fractional order PID controller [FOPID] is designed for automatic blood pressure regulation. One of the most common problems faced by post-operative patients is abnormal blood pressure (BP). Infusion of sodium nitroprusside (SNP) into the patient reduces blood pressure by relaxing the peripheral vasculature's muscles. The patient’s BP must be continuously monitored by an expert and the correct dose has to be given to the patient. It will be difficult to give the desired dosage to a patient manually because drug sensitivity is different for different patients. So, an appropriate controller must be designed to regulate blood pressure and minimize clinical expenses. A fractional-order PID controller is proposed in this paper to regulate mean arterial pressure, and FOPID parameters are optimized as a function of minimizing integral absolute error (IAE), integral squared error (ISE), and integral time absolute error (ITAE) using genetic algorithm. The performance of the proposed system is improved in terms of undershoot, settling time, and maximum peak overshoot. A MATLAB environment was used for the simulation of the system and the implementation of the algorithm.

SAT312 CT-guided Cryoablation Of Hereditary Pheochromocytoma

Abstract Disclosure: E. Griffing: None. B. Reading: None. F. De Luca: None. Background: Guidelines surrounding the management of hereditary pediatric pheochromocytomas (PHEO) are lacking. This is the first report of a pediatric patient with bilateral hereditary PHEO treated with right adrenalectomy and computed tomography (CT) percutaneous-guided cryoablation (CRA) of the left-sided lesion.Clinical case: A previously healthy 15 years-old male presented to a tertiary care hospital with a months-long history of episodic chest pain, flushing, shortness of breath, diaphoresis, and tremulousness. Paternal family history was significant for PHEO and brain stem hemangioblastoma in grandmother and PHEO in the great-grandfather. Targeted familial mutation analysis of the von Hippel-Lindau tumor suppressor gene was positive for pathogenic mutation c.500G>A (p.R167Q). Plasma free normetanephrine level was 4,625 pg/mL (nl: <145 pg/mL), while free metanephrines were normal. Magnetic-resonance imaging of the abdomen visualized a 4.4 x 3.4 x 5.3 cm right adrenal mass and a 1.4 x 1.4 x 1.4 cm left adrenal mass, consistent with bilateral PHEO. He underwent right adrenalectomy after initiation of alpha-receptor blockade and later addition of beta-receptor blockade due to heart rates in the 150’s. After discussion with parents, it was decided to observe the smaller left-sided adrenal lesion. Plasma free normetanephrines initially decreased to 338 pg/mL, but then increased to 507 pg/mL five months post-operatively. Six months after surgery, due to the persistence of hypertension with systolic blood pressure in the 140’s as well as tachycardia with heart rates in the 150’s, he underwent CT-guided CRA of the left-sided PHEO. A 12-minute freeze, 5-minute thaw, and 10-minute freeze, followed by an active thaw were performed. There was an increase in blood pressure during the initial thaw with systolic blood pressure in the 230s, accompanied by bradycardia to the 30s, treated with nitroprusside, phentolamine, and increased sedation. He required continuation of nitroprusside infusion for five hours post-procedure. He was discharged the following day with normal blood pressure and heart rate. He was able to completely wean off anti-hypertensive medications within one month and symptoms of chest pain and tachycardia resolved. In the four years since his procedure, he has not had a recurrence of PHEO nor development of adrenal insufficiency. Plasma free normetanephrines and metanephrines have remained within normal limits. Conclusion: Percutaneous ablation of hereditary PHEO has not been reported before in the pediatric population and may represent a novel treatment strategy that reduces the risk of adrenal insufficiency. Presentation: Saturday, June 17, 2023

Endothelial dysfunction is associated with reduced myocardial mechano-energetic efficiency in drug-naïve hypertensive individuals.

Impaired myocardial mechano-energetics efficiency (MEE) was shown to predict incident heart failure, but pathophysiological mechanisms linking impaired MEE with heart failure have not been elucidated. Endothelial dysfunction is a plausible candidate because it has been associated with heart failure. This study aims to investigate the association between MEE and endothelium-dependent vasodilation, among drug-naïve hypertensive individuals. 198 Drug-naïve hypertensive individuals participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study were included. All participants underwent to an oral glucose tolerance test and to an echocardiogram for myocardial LVM-normalized mechano-energetic efficiency (MEEi) measurement. Endothelial-dependent and endothelial-independent vasodilatation were measured by strain-gauge plethysmography during intra-arterial infusion of acetylcholine and sodium nitroprusside, respectively. A multivariate linear regression analysis was conducted to investigate the independent association between maximal endothelial-dependent vasodilation and MEEi. Maximal ACh-stimulated forearm blood flow (FBF) was associated to decreased myocardial MEEi (β = 0.205, p = 0.002) independently of well-established cardiovascular risk factors including age, sex, BMI, waist circumference, smoking status, total and HDL cholesterol, triglycerides, hsCRP, glucose tolerance status, and HOMA-IR index of insulin resistance. Conversely, no association was observed between SNP-stimulated vasodilation and MEEi. Endothelium-mediated vasodilation may contribute to reduce myocardial MEEi independently of several potential confounders. Because diminished myocardial MEE has been previously associated with incident heart failure, a non-invasive assessment of myocardial MEEi may improve the identification of individuals at higher cardiovascular risk who may benefit from the initiation of pharmacological treatments ameliorating the endothelial dysfunction.

Arterial baroreflex control of heart rate in young and older adults and in patients with heart failure with preserved ejection fraction

Background: The arterial baroreflex (ABR) plays an important role in evoking appropriate cardiovascular adjustments in response to perturbations such as exercise. The ABR control of heart rate (HR) becomes attenuated with advancing age and in a variety of patient populations, but limited information is available in patients with heart failure with preserved ejection fraction (HFpEF). The present study tested the hypothesis that the ABR control of HR is attenuated to a greater extent in patients with HFpEF compared to older and young controls. Methods: Six patients with HFpEF (71±6 years; 35.3±6.6 kg/m2), 4 older controls (68±4 years; 25.1±3.4 kg/m2), and 7 young controls (27±4 years; 26.6±3.9 kg/m2) underwent sequential bolus infusions of sodium nitroprusside (50-100 μg) and phenylephrine (150 μg) (modified Oxford technique) to provoke acute hypotension (“BP falls”) and hypertension (“BP rises”), respectively. Cardiac baroreflex gain was quantified as the weighted linear regression slope between the R-R interval and systolic blood pressure (BP). Results: Compared to young controls (10.7±3.4 ms/mmHg), overall cardiac baroreflex gain was reduced in older controls (3.4±1.6 ms/mmHg) and patients with HFpEF (2.1±1.8 ms/mmHg) (p<0.05), with no difference between the older controls and patients with HFpEF (p=0.718). During BP falls, cardiac baroreflex gain was not different between groups (p=0.06), but was qualitatively lower in patients with HFpEF (0.6±1.5 ms/mmHg) compared to young (5.3±5.5 ms/mmHg) and older controls (5.2±1.9 ms/mmHg). During BP rises, cardiac baroreflex gain was not different between older controls (2.6±0.8 ms/mmHg) and patients with HFpEF (2.3±2.0 ms/mmHg) (p>0.05); however, responses in patients with HFpEF were attenuated compared to young controls 10.7±5.8 ms/mmHg) (p<0.05). Conclusion: These findings suggest an age-related attenuation in the overall ARB control of HR that does not appear to be further exacerbated in patients with HFpEF. However, patients with HFpEF may exhibit a selective attenuation in ABR-mediated tachycardia in response to acute reductions in BP that may pose an increased risk of hypotension and frank syncope. This work was funded in part by the U.S. Department of Veterans Affairs (RX001311, to D.W.W.; IK2RX003670, to K.B.). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

SHDB mutant functional metastatic paraganglioma: The efficacy of Lutetium-177 DOTATE

Abstract Introduction Therapeutic options for metastatic paraganglioma (PGL) are limited, especially in the presence of uncontrolled secondary hypertension (HTN). Early findings from Lutetium-177 (Lu-177) DOTATE show promise for efficacy, although data on HTN control and survival are uncertain. Herein, we presented the successful treatment of a patient with metastatic PGL and uncontrolled HTN with Lu-177 DOTATE. Clinical Case A 16-year-old woman was admitted to the emergency department with severe headache, nausea and vomiting. She also reported stomach and low back pain for three months. The patient's blood pressure was 220/140 mmHg and a sodium nitroprusside infusion was started to treat the hypertensive crisis. On physical examination she had abdominal tenderness. A computer tomography (CT) examination revealed 6 cm mass, multiple metastatic nodular lesions in the lung and liver, as well as lytic lesions in all bones, and metastatic lymph nodes in thorax and abdomen. She is referred to our department for further evaluation HTN. Laboratory examinations revealed that plasma norepinephrine 24926 ng/L (70–480), 24-hour urine norepinephrine 1335 µg/day (20–81), metanephrine 534 µg/day (52–341), 3-metoksitiramine 771 µg/day (0–451), normetanephrine 20456 µg/day (88–444). Other laboratory findings were normal range. MIBG I131 scan which showed pathological uptake of MIBG was demonstrated in the regions described on CT. Genetic panel by next-generation sequencing (NGS) identify germline mutation and she had heterozygous mutations in SHDB (c.725 G>A) and BUB1B (c.1378 C>T). Surgical treatment was performed, and pathological finding reported 6cm mass, Ki-67 labeling index: %2, chromogranin A diffuse positive and there was vascular invasion. It was confirmed to be malignant PGL. 131I-MIBG therapy couldn't be given because of drugs interaction that used by patient. She received 13 cycles chemotherapy (cyclophosphamide, vincristine, dacarbazine) and palliative radiotherapy to metastatic bone lesions. She continued, however, to suffer from low back pain and HTN. Rising plasma and urine catecholamine levels. Therefore, conventional chemotherapy had been discontinued and he was commenced on Lu-DOTATATE therapy. Up to now, she has received 2 cycles at intervals of three months. Her clinical response was excellent with gradual improvement of symptoms and quality of life. Blood pressure is now within normal values without medication. There was significant reduction in the size of overall metastatic disease on Ga-68 DOTATE scanning. Conclusion Lu-177 DOTATE has potential advantages (drug interaction, radiation-safety) compared with 131I-MIBG therapy and chemotherapy. Our case demonstrates significant clinical and biochemical success in patients with metastatic PGL in addition to excellent disease management with low toxicity from PRRT. Lu-177 DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic PGL.

The Hemodynamic-Stabilizing Properties of Dexmedetomidine on Adrenalectomy For Pheochromocytoma: A Case Report

Pheochromocytoma is a catecholamine-secreting neuroendocrine tumor and represents a challenge to the anesthesiologist. Without adequate preoperative preparation, excessive catecholamine release can result in life-threatening cardiovascular complications. To control blood pressure during the surgery, an infusion of sodium nitroprusside and dexmedetomidine was administered. Dexmedetomidine helps prevent hemodynamic instability during the tumor resection and was a way of interrupting the catecholamine release. This report attempts to address the preoperative and intraoperative issues in managing these challenging tumors with an emphasis on other therapeutic options to control the adrenergic crisis during the surgery.

602 CRITICAL AORTIC STENOSIS IN PROFOUND CARDIOGENIC SHOCH: BRIDGE TO TAVI WITH LEVOSIMENDAN.

Abstract Cardiogenic shock (CS) in severe aortic stenosis (AS) is associated with high mortality. Percutaneous aortic valve implantation (TAVI) is a possible definite solution, but generally it cannot be performed on an emergency base. In patients with severe systolic dysfunction an augmentation of cardiac index (CI) during dobutamine and nitroprusside infusion can demonstrate contractile and afterload reserve. Invasive hemodynamic monitoring is necessary to keep optimal filling pressure and verify arterial pressure stability. If the hemodynamic response is positive we administer levosimendan to bridge the patient to decision and/or to TAVI. In our small experience this strategy is efficacy and well tolerated.

677 PREDICTION OF RIGHT VENTRICULAR FAILURE AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION: ROLE OF VASODILATOR CHALLENGE

Abstract Pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation. Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve. Patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients who had undergone RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental, and haemodynamic parameters, at baseline and after nitroprusside infusion and evaluated potential associations with post-LVAD RVF. Of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. Fractional area change (FAC) (OR: 0.647, CI: 0.481–0.871; P = 0.004), pulmonary artery systolic pressure (PASP)(OR: 0.856, CI: 0.761–0.964; P=0.010), and post-sodium nitroprusside (NTP) PAPi (OR: 0.218, CI: 0.073–0.653; P = 0.006) were independent predictors of post-LVAD RVF. The model combining FAC, PASP, and post-NTP PAPi demonstrated a predictive accuracy of 90.7%. Addition of post-NTP PAPi significantly increased the predictive accuracy of the European Registry for Patients with Mechanical Circulatory Support right-sided heart failure risk score [79.4 vs. 70.4%; area under the curve (AUC): 0.841 vs. 0.724, P = 0.022] and the CRITT score (79.6% vs. 74%; AUC: 0.861 vs. 0.767 P = 0.033). Post-NTP PAPi has observed to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi using a vasodilator challenge may represent a method of testing RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed to confirm this hypothesis.