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Cardiovascular Research Jul 2023Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of the metabolic alterations is complex and likely dependent on the...
AIMS
Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of the metabolic alterations is complex and likely dependent on the particular stage of HF progression. Vascular endothelial growth factor B (VEGF-B) has been shown to modulate metabolic processes and to induce physiological cardiac hypertrophy; thus, it could be cardioprotective in the failing myocardium. This study investigates the role of VEGF-B in cardiac proteomic and metabolic adaptation in HF during aldosterone and high-salt hypertensive challenges.
METHODS AND RESULTS
Male rats overexpressing the cardiac-specific VEGF-B transgene (VEGF-B TG) were treated for 3 or 6 weeks with deoxycorticosterone-acetate combined with a high-salt (HS) diet (DOCA + HS) to induce hypertension and cardiac damage. Extensive longitudinal echocardiographic studies of HF progression were conducted, starting at baseline. Sham-treated rats served as controls. To evaluate the metabolic alterations associated with HF, cardiac proteomics by mass spectrometry was performed. Hypertrophic non-treated VEGF-B TG hearts demonstrated high oxygen and adenosine triphosphate (ATP) demand with early onset of diastolic dysfunction. Administration of DOCA + HS to VEGF-B TG rats for 6 weeks amplified the progression from cardiac hypertrophy to HF, with a drastic drop in heart ATP concentration. Dobutamine stress echocardiographic analyses uncovered a significantly impaired systolic reserve. Mechanistically, the hallmark of the failing TG heart was an abnormal energy metabolism with decreased mitochondrial ATP, preceding the attenuated cardiac performance and leading to systolic HF.
CONCLUSIONS
This study shows that the VEGF-B TG accelerates metabolic maladaptation which precedes structural cardiomyopathy in experimental hypertension and ultimately leads to systolic HF.
Topics: Rats; Male; Animals; Vascular Endothelial Growth Factor B; Desoxycorticosterone Acetate; Heart Failure, Systolic; Proteomics; Hypertension; Myocardium; Heart Failure; Cardiomegaly
PubMed: 36951047
DOI: 10.1093/cvr/cvad040 -
Animals : An Open Access Journal From... Sep 2023This retrospective study investigated the effect of a xylazine infusion on heart rate; mean arterial pressure; blood gases; anesthetic and dobutamine requirements;...
This retrospective study investigated the effect of a xylazine infusion on heart rate; mean arterial pressure; blood gases; anesthetic and dobutamine requirements; recovery quality and duration; percentage of death/survival; and days to die/discharge in horses after colic surgery under partial intravenous anesthesia with isoflurane and lidocaine infusion. Anesthetic records of equine colic surgery were reviewed from similar periods in 2020-2021 and 2021-2022. In both groups, after sedation with xylazine 0.7 mg/kg intravenously (IV) and induction with ketamine 2.2 mg/kg and midazolam 0.06 mg/kg IV, anesthesia was maintained with isoflurane and lidocaine (bolus 1.5 mg/kg IV, infusion 2 mg/kg/h). Group L (2020-2021, = 45) received xylazine 0.2 mg/kg IV before recovery, group XL (2021-2022, = 44) received xylazine 0.5 mg/kg/h IV intraoperatively. In group XL, minimal ( = 0.04) and average ( = 0.04) heart rate, intraoperative hematocrit ( = 0.001), minimal ( = 0.002) and maximal ( = 0.04) dobutamine administration rate, animals requiring ketamine top-ups ( = 0.04), and the number of days to discharge ( = 0.02), were significantly lower compared to group L. During recovery in group XL, the time to sternal recumbency ( = 0.03) and time to first attempt ( = 0.04) were significantly longer. This retrospective study suggests that a xylazine infusion may have beneficial effects on horses undergoing colic surgery. Further prospective studies are necessary.
PubMed: 37760302
DOI: 10.3390/ani13182902 -
Cureus Feb 2024The aim of this systematic review and meta-analysis was to compare the outcomes between milrinone and dobutamine in patients with cardiogenic shock. The search strategy... (Review)
Review
The aim of this systematic review and meta-analysis was to compare the outcomes between milrinone and dobutamine in patients with cardiogenic shock. The search strategy involved a comprehensive exploration of electronic databases, including PubMed, EMBASE, Cochrane Library, and Scopus from the the inception of each database up to the 31st of January 2024. A combination of keywords and Medical Subject Headings (MeSH) terms was employed to identify relevant studies. The outcomes assessed in this meta-analysis included all-cause in-hospital mortality, length of intensive care unit (ICU stay), and length of hospital stay. A total of seven studies were included in this meta-analysis enrolling 3,841 patients (2,331 in the dobutamine group and 1,510 in the milrinone group). Pooled analysis showed that the risk of all-cause mortality was significantly higher in patients receiving dobutamine compared to patients receiving milrinone (relative risk (RR): 1.43, 95% confidence interval (CI): 1.02 to 2.01, p-value: 0.04). However, the length of hospital stay and length of ICU stay were not significantly different between the two groups. Limited data are available to favor the use of one inotropic agent over another. Dobutamine might lead to a shorter hospital length of stay, but there is also a risk of increased all-cause mortality. Larger randomized studies with adequate power are needed to validate these observations.
PubMed: 38544600
DOI: 10.7759/cureus.54948 -
JMIR Research Protocols Nov 2023Breast reconstruction is an integral part of breast cancer care. There are 2 main types of breast reconstruction: alloplastic (using implants) and autologous (using the...
Dobutamine and Goal-Directed Fluid Therapy for Improving Tissue Oxygenation in Deep Inferior Epigastric Perforator (DIEP) Flap Breast Reconstruction Surgery: Protocol for a Randomized Controlled Trial.
BACKGROUND
Breast reconstruction is an integral part of breast cancer care. There are 2 main types of breast reconstruction: alloplastic (using implants) and autologous (using the patient's own tissue). The latter creates a more natural breast mound and avoids the long-term need for surgical revision-more often associated with implant-based surgery. The deep inferior epigastric perforator (DIEP) flap is considered the gold standard approach in autologous breast reconstruction. However, complications do occur with DIEP flap surgery and can stem from poor flap tissue perfusion/oxygenation. Hence, the development of strategies to enhance flap perfusion (eg, goal-directed perioperative fluid therapy) is essential. Current perioperative fluid therapy is traditionally guided by subjective criteria, which leads to wide variations in clinical practice.
OBJECTIVE
The main objective of this trial is to determine whether the use of minimally invasive cardiac output (CO) monitoring for guiding intravenous fluid administration, combined with low-dose dobutamine infusion (via a treatment algorithm), will increase tissue oxygenation in patients undergoing DIEP flap surgery.
METHODS
With appropriate institutional ethics board and Health Canada approval, patients undergoing DIEP flap surgery are randomly assigned to receive CO monitoring for the guidance of intraoperative fluid therapy in addition to a low-dose dobutamine infusion (which potentially improves flap oxygenation) versus the current standard of care. The primary outcome is tissue oxygenation measured via near-infrared spectroscopy at the perfusion zone furthest from the perforator vessels 45 minutes after vascular reanastomosis of the DIEP flap. Low dose (2.5 μg/kg/hr) dobutamine infusion continues for up to 4 hours postoperatively, provided there are no associated complications (ie, persistent tachycardia). Flap oxygenation, hemodynamic parameters, and any medication-associated side effects/complications are monitored for up to 48 hours postoperatively. Complications, rehospitalizations, and patient satisfaction are also collected until 30 days postoperatively.
RESULTS
Funding and regulatory approvals were obtained in 2019, but the study recruitment was interrupted by the COVID-19 pandemic. As of October 4, 2023, 34 participants have been recruited. Because of the significant delays associated with the pandemic, the expected completion date was extended. We expect the study to be completed and ready for potential news release (as appropriate) and publication by July 2024. No patients have suffered any adverse effects/complications from participating in this study, and none have been lost to follow-up.
CONCLUSIONS
CO-directed fluid therapy in combination with a low-dose dobutamine infusion via a treatment algorithm has the potential to improve DIEP flap tissue oxygenation and reduce complications following DIEP flap breast reconstruction surgery. However, given that the investigators remain blinded to group randomization, no comment can be made regarding the efficacy of this intervention for improving tissue oxygenation at this time. Nevertheless, no patients have been withdrawn for safety concerns thus far, and compliance remains high.
TRIAL REGISTRATION
Clinicaltrials.gov NCT04020172; https://clinicaltrials.gov/study/NCT04020172.
PubMed: 37991835
DOI: 10.2196/48576 -
Journal of Nuclear Cardiology :... May 2024Data on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine...
BACKGROUND
Data on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine reducing stress perfusion.
METHOD
Consecutive LT candidates (n = 114) undergoing cardiac rest/stress PET were instructed to abstain from caffeine for 2 days extended to 5 and 7 days. Due to persistently high prevalence of measurable blood caffeine after 5-day caffeine abstinence, dipyridamole (n = 41) initially used was changed to dobutamine (n = 73). Associations of absolute flow, coronary flow reserve (CFR), detectable blood caffeine, and Modified End-Stage Liver Disease (MELD) score for liver failure severity were evaluated. Coronary flow data of LT candidates were compared to non-LT control group (n = 102 for dipyridamole, n = 29 for dobutamine).
RESULTS
Prevalence of patients with detectable blood caffeine was 63.3%, 36.7% and 33.3% after 2-, 5- and 7-day of caffeine abstinence, respectively. MELD score was associated with detectable caffeine (odd ratio 1.18,P < 0.001). CFR was higher during dipyridamole stress without-caffeine versus with-caffeine (2.22 ± 0.80 vs 1.55 ± 0.37,P = 0.048) but lower than dobutamine stress (2.22 ± 0.80 vs 2.82 ± 1.02,P = 0.026). Mediation analysis suggested that the dominant association between CFR and MELD score in dipyridamole group derived from caffeine-impaired CFR and liver failure/caffeine interaction. CFR in LT candidates was lower than non-LT control population in both dipyridamole and dobutamine group.
CONCLUSION
We demonstrate exceptionally high prevalence of detectable blood caffeine in LT candidates undergoing stress PET myocardial perfusion imaging resulting in reduced CFR with dipyridamole compared to dobutamine. The delayed caffeine clearance in LT candidates makes dobutamine a preferred stress agent in this population.
PubMed: 38761831
DOI: 10.1016/j.nuclcard.2024.101884 -
Journal of Medical Cases May 2024This study presents a case of norepinephrine and dobutamine-induced dynamic left ventricular outflow tract obstruction (LVOTO) caused by systolic anterior motion (SAM)...
This study presents a case of norepinephrine and dobutamine-induced dynamic left ventricular outflow tract obstruction (LVOTO) caused by systolic anterior motion (SAM) in a patient experiencing acute anterior myocardial infarction (MI). In a 76-year-old patient presenting with acute MI, intensive use of norepinephrine and dobutamine may lead to the development of dynamic LVOTO and SAM. The presence of hypotension and a new cardiac murmur may suggest a mechanical complication such as acute mitral regurgitation (MR) or ventricular septal rupture (VSR). The assessment of the left ventricular outflow tract (LVOT) using echocardiography plays a critical role in the diagnosis of SAM and its associated MR and dynamic LVOTO. The patient's condition was stabilized through the cessation of inotropes and the implementation of aggressive fluid resuscitation, resulting in improved hemodynamics. In conclusion, prompt identification of the underlying pathophysiological mechanisms is imperative for effectively managing this condition and preventing hemodynamic exacerbation.
PubMed: 38715913
DOI: 10.14740/jmc4204 -
Frontiers in Cardiovascular Medicine 2023Patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF) have a heterogeneous prognosis, and assessment of coronary physiology with...
BACKGROUND AND AIMS
Patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF) have a heterogeneous prognosis, and assessment of coronary physiology with coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) may complement established predictors based on wall motion and EF.
METHODS AND RESULTS
In a prospective multicenter study design, we enrolled 1,408 HF patients (age 66 ± 12 years, 1,035 men), with EF <50%, 743 (53%) with coronary artery disease, and 665 (47%) with normal coronary arteries. Recruitment (years 2004-2022) involved 8 accredited laboratories, with inter-observer variability <10% for CFV measurement. Baseline CFV (abnormal value >31 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. CFVR (abnormal value ≤2.0) was assessed with exercise ( = 99), dobutamine ( = 100), and vasodilator stress (dipyridamole in 1,149, adenosine in 60). Inducible myocardial ischemia was identified with wall motion score index (WMSI) stress > rest (cut-off Δ ≥ 0.12). LV contractile reserve (CR) was identified with WMSI stress < rest (cutoff Δ ≥ 0.25). Test response ranged from score 0 (EF > 30%, CFV ≥ 32 cm/s, CFVR > 2.0, LVCR present, ischemia absent) to score 5 (all steps abnormal). All-cause death was the only endpoint. Results. During a median follow-up of 990 days, 253 patients died. Independent predictors of death were EF (HR: 0.956, 95% CI: 0.943-0.968, < 0.0001), CFV (HR: 2.407, 95% CI: 1.871-3.096, < 0.001), CFVR (HR: 3.908, 95% CI: 2.903-5.260, < 0.001), stress-induced ischemia (HR: 2.223, 95% CI: 1.642-3.009, < 0.001), and LVCR (HR: 0.524, 95% CI: 0.324-.647, = 0.008). The annual mortality rate was lowest (1.2%) in patients with a score of 0 (= 61) and highest (31.9%) in patients with a score of 5 ( = 15, < 0.001).
CONCLUSION
High resting CFV is associated with worse survival in ischemic and nonischemic HF with reduced EF. The value is independent and additive to resting EF, CFVR, LVCR, and inducible ischemia.
PubMed: 38075970
DOI: 10.3389/fcvm.2023.1290366 -
Health Science Reports Mar 2024Free flap reconstruction for head and neck cancer is associated with a high risk of perioperative complications. One of the modifiable risk factors associated with...
BACKGROUND
Free flap reconstruction for head and neck cancer is associated with a high risk of perioperative complications. One of the modifiable risk factors associated with perioperative morbidity is intraoperative hypotension (IOH). The main aim of this pilot study is to determine if the intraoperative use of goal-directed hemodynamic therapy (GDHT) is associated with a reduction in the number of IOH events in this population.
METHODS
A before-and-after study design. The patients who had intraoperative GDHT were compared to patients from a previous period before the implementation of GDHT. The primary outcome was the number of IOH episodes defined as five or more successive minutes with a mean arterial pressure <65 mmHg. The secondary outcomes included major postoperative morbidity and 30-day mortality.
RESULTS
A total of 414 patients were included. These were divided into two groups. The control group ( = 346; January 1, 2018, to December 31, 2019), and the monitored group ( = 68; January 1, 2020, to May 1, 2021). The median intraoperative administered fluid volume was similar between the control and monitored groups (2250 interquartile range [IQR] [1607-3050] vs. 2210 IQR [1700-2807] mL). The monitored group was found to have an increased use of norepinephrine and dobutamine (respectively, 1.2% vs. 5.9% and 2.4% vs. 30.9%; < 0.05). When adjusting for confounders (comorbidities, estimated blood loss, and duration of anesthesia) the incidence rate ratio (95% confidence interval) of number of IOH events was 0.94 (0.86-1.03), = 0.24. The rate of postoperative flap and medical complications did not differ between the two groups.
CONCLUSIONS
Even though the use of vasopressors/inotropes was higher in the monitored group, the number of IOH episodes and postoperative morbidity and mortality were similar between the two groups. Further change in hemodynamic management will require the use of specific blood pressure targets in the GDHT fluid algorithm.
PubMed: 38524770
DOI: 10.1002/hsr2.1943 -
Biomedicines May 2024Hypovolemic shock is a circulatory failure, due to a loss in the effective circulating blood volume, that causes tissue hypoperfusion and hypoxia. This condition...
Hypovolemic shock is a circulatory failure, due to a loss in the effective circulating blood volume, that causes tissue hypoperfusion and hypoxia. This condition stimulates reactive oxygen species (ROS) and pro-inflammatory cytokine production in different organs and also in the central nervous system (CNS). Levosimendan, a cardioprotective inodilator, and dobutamine, a β1-adrenergic agonist, are commonly used for the treatment of hypovolemic shock, thanks to their anti-inflammatory and antioxidant effects. For this reason, we aimed at investigating levosimendan and dobutamine's neuroprotective effects in an "in vitro" model of lipopolysaccharide (LPS)-induced neuroinflammation. Human microglial cells (HMC3) were challenged with LPS (0.1 µg/mL) to induce an inflammatory phenotype and then treated with levosimendan (10 µM) or dobutamine (50 µM) for 24 h. Levosimendan and dobutamine significantly reduced the ROS levels and markedly increased Nrf2 and HO-1 protein expression in LPS-challenged cells. Levosimendan and dobutamine also decreased p-NF-κB expression and turned off the NLRP3 inflammasome together with its downstream signals, caspase-1 and IL-1β. Moreover, a reduction in TNF-α and IL-6 expression and an increase in IL-10 levels in LPS-stimulated HMC3 cells was observed following treatment. In conclusion, levosimendan and dobutamine attenuated LPS-induced neuroinflammation through NF-κB pathway inhibition and NLRP3 inflammasome activation via Nrf2/HO-1 signalling, suggesting that these drugs could represent a promising therapeutic approach for the treatment of neuroinflammation consequent to hypovolemic shock.
PubMed: 38790971
DOI: 10.3390/biomedicines12051009 -
Veterinary Sciences Feb 2024Horses undergoing abdominal exploratory surgery are at risk of hypotension and hypoperfusion. Normal mean arterial pressure is used as a surrogate for adequate tissue...
Horses undergoing abdominal exploratory surgery are at risk of hypotension and hypoperfusion. Normal mean arterial pressure is used as a surrogate for adequate tissue perfusion. However, measures of systemic circulation may not be reflective of microcirculation. This study measured the mean arterial pressure, cardiac index, lactate, and four microcirculatory indices in six healthy, anesthetized adult horses undergoing elective laparotomies. The microcirculatory parameters were measured at three different sites along the gastrointestinal tract (oral mucosa, colonic serosa, and rectal mucosa) with dark-field microscopy. All macro- and microcirculatory parameters were obtained when the horses were normotensive, hypotensive, and when normotension returned following treatment with dobutamine. Hypotension was induced with increases in inhaled isoflurane. The horses successfully induced into hypotension did not demonstrate consistent, expected changes in systemic perfusion or microvascular perfusion parameters at any of the three measured gastrointestinal sites. Normotension was successfully restored with the use of dobutamine, while the systemic perfusion and microvascular perfusion parameters remained relatively unchanged. These findings suggest that the use of mean arterial pressure to make clinical decisions regarding perfusion may or may not be accurate.
PubMed: 38393113
DOI: 10.3390/vetsci11020095