Muscle breakdown determines Arginine (ARG) availability during hyperdynamic sepsis in the pig

A chronic canine model of hyperdynamic sepsis was achieved by cecal ligation and puncture (SEP) in conjunction with continuous high-volume fluid resuscitation. Cardiac function was evaluated using ultrasonic cardiac crystals placed across the major, minor, and wall thickness axes of the left ventricle, together with simultaneous arterial and ventricular pressure measurement. Seven to 10 days after crystal implantation, animals were randomized to either SEP (n = 10) or sham laparotomy control (n = 7). SEP dogs became febrile and lethargic, with elevated leukocyte counts and positive blood cultures for enteric organisms. They were also hyperdynamic, with significant increases in heart rate and cardiac output and a fall in systemic vascular resistance. Systolic blood pressure, stroke volume, and ejection fraction remained stable. Relative to control, the SEP group demonstrated a significant reduction in intrinsic contractility during systole, as measured by the heart rate and load-independent index of left ventricular performance Emax (P less than 0.01), confirming the observations of others. In addition, however, diastolic function also became markedly abnormal with a progressive increase in unstressed and end-diastolic ventricular volumes (P less than 0.05) and a significant decrease in myocardial compliance as quantitated by transmural pressure vs. volume-strain analysis. It is hypothesized that this increase in diastolic volume helps to maintain global cardiac performance during the hyperdynamic response to sepsis in the presence of adequate volume support.

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Update Review about Metabolic Myopathies

Life ◽

10.3390/life10040043 ◽

2020 ◽

Vol 10 (4) ◽

pp. 43

Author(s):

Josef Finsterer

Keyword(s):

Cell Metabolism ◽

Neuromuscular Disorders ◽

Age At Onset ◽

Respiratory Muscles ◽

Exercise Intolerance ◽

Axial Muscles ◽

Sequencing Technologies ◽

Metabolic Myopathies ◽

Muscle Breakdown ◽

Enzymatic Pathways

The aim of this review is to summarize and discuss recent findings and new insights in the etiology and phenotype of metabolic myopathies. The review relies on a systematic literature review of recent publications. Metabolic myopathies are a heterogeneous group of disorders characterized by mostly inherited defects of enzymatic pathways involved in muscle cell metabolism. Metabolic myopathies present with either permanent (fixed) or episodic abnormalities, such as weakness, wasting, exercise-intolerance, myalgia, or an increase of muscle breakdown products (creatine-kinase, myoglobin) during exercise. Though limb and respiratory muscles are most frequently affected, facial, extra-ocular, and axial muscles may be occasionally also involved. Age at onset and prognosis vary considerably. There are multiple disease mechanisms and the pathophysiology is complex. Genes most recently related to metabolic myopathy include PGM1, GYG1, RBCK1, VMA21, MTO1, KARS, and ISCA2. The number of metabolic myopathies is steadily increasing. There is limited evidence from the literature that could guide diagnosis and treatment of metabolic myopathies. Treatment is limited to mainly non-invasive or invasive symptomatic measures. In conclusion, the field of metabolic myopathies is evolving with the more widespread availability and application of next generation sequencing technologies worldwide. This will broaden the knowledge about pathophysiology and putative therapeutic strategies for this group of neuromuscular disorders.

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An Outbreak of Muscle Breakdown

Current Sports Medicine Reports ◽

10.1249/jsr.0b013e3181fc6d1a ◽

2010 ◽

Vol 9 (6) ◽

pp. 325-326 ◽

Cited By ~ 5

Author(s):

E. Randy Eichner

Keyword(s):

Muscle Breakdown

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Effects of Renal Denervation on Regional Hemodynamics and Kidney Function in Experimental Hyperdynamic Sepsis

Critical Care Medicine ◽

10.1097/ccm.0000000000000302 ◽

2014 ◽

Vol 42 (6) ◽

pp. e401-e409 ◽

Cited By ~ 14

Author(s):

Paolo Calzavacca ◽

Michael Bailey ◽

Elena Velkoska ◽

Louise M. Burrell ◽

Rohit Ramchandra ◽

...

Keyword(s):

Kidney Function ◽

Renal Denervation ◽

Regional Hemodynamics ◽

Hyperdynamic Sepsis

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Interaction between pyridine nucleotide coenzymes and heme proteins as a possible source of error in assay of activities of coenzyme-linked enzyme.

Clinical Chemistry ◽

10.1093/clinchem/35.10.2129 ◽

1989 ◽

Vol 35 (10) ◽

pp. 2129-2133 ◽

Cited By ~ 1

Author(s):

M D Jeyasingham ◽

O E Pratt ◽

H K Roopral

Keyword(s):

Pyridine Nucleotide ◽

Peak Height ◽

Heme Group ◽

Ultraviolet Absorbance ◽

The Third ◽

Spectral Shifts ◽

Muscle Breakdown ◽

Activity Of Enzymes ◽

Source Of Error ◽

Absorbance Spectra

Abstract The ultraviolet absorbance spectra of pyridine nucleotide coenzymes change in the presence of heme-containing proteins. The positions of each of the two main absorbance peaks of NADH are shifted progressively towards shorter wavelengths in the presence of increasing concentrations of hemoglobin, and the third peak, at 220 nm, disappears altogether. Similar changes are seen in the spectra of NAD+ and NADPH, and similar effects on these spectra are produced by myoglobin and cytochrome c, but not by comparable concentrations of albumin. The spectral shifts are generally accompanied by a decreased peak height. This finding may help explain problems reported by previous workers in the measurement of the activity of enzymes such as transketolase or lactate dehydrogenase in erythrocyte hemolysates. Errors may be considerable if allowance is not made for this effect, especially if the concentration of heme protein in the spectrophotometer cuvette much exceeds 1 g/L. The interaction appears to indicate some form of bonding, occurring generally between pyridine nucleotide coenzymes and the heme group in proteins. We relate the findings to measurement of activities of pyridine nucleotide-linked enzymes in erythrocyte lysates and in plasma containing myoglobin after muscle breakdown.

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Pyridoxalated hemoglobin polyoxyethylene conjugate reverses hyperdynamic circulation in septic sheep

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.6.1991 ◽

1998 ◽

Vol 84 (6) ◽

pp. 1991-1999 ◽

Cited By ~ 24

Author(s):

Hans G. Bone ◽

Paul J. Schenarts ◽

Stefanie R. Fischer ◽

Roy McGuire ◽

Lillian D. Traber ◽

...

Keyword(s):

Blood Flow ◽

Regional Blood Flow ◽

Recovery Period ◽

Resistance Index ◽

Blood Chemistry ◽

Control Group ◽

Hyperdynamic Circulation ◽

Baseline Values ◽

And Function ◽

Hyperdynamic Sepsis

We investigated the effects of modified hemoglobin on regional blood flow and function of different organs during hyperdynamic sepsis. Fourteen sheep were surgically prepared for the study. After a 5-day recovery period, a continuous infusion of live Pseudomonas aeruginosa bacteria was begun and maintained for 48 h. At 24 h, after a hyperdynamic circulation had developed, the animals were randomly assigned to two groups: 1) a treatment group ( n = 7) that received an infusion with 100 mg/kg pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) over 30 min and 2) a control group ( n = 7) that received only the vehicle. PHP infusion increased mean arterial pressure from 86 ± 2.8 to 101.8 ± 3.5 mmHg ( P < 0.05) and systemic vascular resistance index from 769 ± 42.1 to 1,087 ± 56.8 dyn ⋅ s ⋅ m2⋅ cm−5( P < 0.05). PHP infusion did not decrease regional blood flow, measured with fluorescent microspheres, below the baseline values in any of the analyzed tissues. None of the investigated blood chemistry variables showed any changes indicative of impaired organ function after PHP infusion. In our model of ovine sepsis we found no side effects after PHP infusion that would limit the use of PHP as a nitric oxide scavenger in sepsis.

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