The CarCO Stress Model – Step-by-Step Mechanism

THE CARCO STRESS MODEL: Carbon Monoxide Exposure → Peroxynitrite Formation in Capillaries → Fibrin Amyloid Formation → Microvascular Obstruction → Reduced Mitochondrial Oxygen Availability → Aerobic Energy Production Failure → Systemic Dysfunctions

1. Carbon Monoxide Enters the Bloodstream

Carbon monoxide enters the lungs with inhaled air and passes across the lung surface into the bloodstream. Most carbon monoxide binds to hemoglobin inside red blood cells. A smaller fraction remains physically dissolved in the blood plasma.

2. Carbon Monoxide Reaches the Microcirculation

The circulation carries both red-blood-cell-bound and plasma-dissolved carbon monoxide throughout the body. As blood flows into the arterioles and capillaries, carbon monoxide dissolved in the plasma circulates outside the red blood cells. This dissolved state allows the gas to interact directly with various cellular and molecular components in the bloodstream.

3. Peroxynitrite Formation

In platelet-neutrophil complexes, carbon monoxide binds to heme proteins in platelets and displaces nitric oxide. The released nitric oxide then reacts rapidly with superoxide present in the local environment, producing peroxynitrite (ONOO⁻).

4. Immune Cell activation

Peroxynitrite triggers neutrophils to release neutrophil extracellular traps (NETs). These are physical web-like structures containing neutrophil DNA and proteins such as myeloperoxidase (MPO) and neutrophil elastase.

5. Fibrin Amyloid Formation

Carbon monoxide bound to heme iron and NET interact with circulating fibrinogen, forming strong amyloid structures. This abnormal structure attracts platelets and resists normal physiological breakdown.

6. Fibrin Amyloids Impair Microcirculation

Repeated exposure sustains ongoing fibrinogen amyloid formation, progressively obstructing more microvessels. As fewer pathways remain open, red blood cells can no longer reach all the capillaries. This prevents oxygen from transferring into the surrounding tissues, causing a progressive decline in tissue oxygen delivery.

The Impact of Acute Infections

During a major infection, the body produces an excessive number of platelet-neutrophil complexes. When activated by carbon monoxide, this sharply increases fibrinogen amyloid formation. The resulting severe microvascular obstruction can trigger the sudden onset of chronic conditions (Long Covid, ME-CFS).

7. Microvascular Obstruction leads to energy production failure

When enough microvessels become obstructed, cells do not receive sufficient oxygen. Mitochondrial ATP production falls, forcing cells to rely on anaerobic energy production. This shift is highly inefficient, depleting cellular energy reserves, accumulating metabolic by-products, and preventing normal cellular repair and function.

8. Failure of Oxygen-Dependent Body Systems

Because biological processes require a constant supply of energy, this chronic disruption impairs every bodily system that depends on an optimal oxygen supply. This continuous deterioration directly causes the development of various systemic diseases and medical conditions.

9. Microvascular Blockages Weaken Immune Defence and Promote Chronic Inflammation

Fibrin amyloid blockages can narrow microvessels enough to prevent large circulating white blood cells from reaching affected tissues, while much smaller bacteria, viruses, or microbial particles may still reach the same areas. This can leave tissues without normal local immune-cell protection, impair pathogen clearance, and allow infections and inflammatory activity to persist.

This continuous biological chain demonstrates how carbon monoxide exposure can translate into structural vascular damage, impaired immune defence, chronic inflammation, and systemic metabolic failure.